Qimr2004 2005

1945 – 2005

6 0 t h A nnual Report

Our Vision

Corporate Structure

To be a world renowned medical research institution

Minister for Health Queensland Government

Our Mission Better health through medical research

QIMR Council

Our Philosophy

Director

The QIMR logo is comprised of superimposed benzene rings which symbolise one of the fundamental molecular arrangements of the chemicals which make up living things

Our Diamond Jubilee This year, QIMR celebrates 60 years of medical research for Queensland.

To commemorate this Diamond Jubilee year, QIMR has adopted a motif which transforms the benzenes of our ofďŹ cial logo into gemstones

Secretary and Chief Operating OfďŹ cer

QIMR supports scientists who perform world-class medical research aimed at improving the health and well-being of all people

Our Logo

QIMR Trust

Deputy Director

Assistant Directors

Development and Marketing Department

Infectious Diseases and Immunology Division

Corporate Division

Cancer and Cell Biology Division

Population Studies and Human Genetics Division

Indigenous Health Research Program

Therapeutic Development and Clinical Research Division

Contents

Chairman’s Report

2

Council members

3

From the Director

5

A Celebration of 60 Years

8

Research

Queensland Institute of Medical Research

12

Infectious Diseases and Immunology

13

Cancer and Cell Biology

34

Population Studies and Human Genetics

47

Indigenous Health Research Program

54

Therapeutic Development and Clinical Trials

56

Joint Programs

59

Spin-Off Companies

61

Corporate Division

63

Committees

66

Development and Marketing

68

Postgraduate Training

69

Education Program

73

Awards

74

Grants and Funding

77

Publications

80

Invited Lectures and Presentations

88

Trust Report

92

Trust Members

93

Donors to the Institute

95

Staff

100

Research Students at QIMR

104

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Chairman’s Report Sir Bruce Watson, BE (Elec) B Com

QIMR has become a household name in Queensland as an internationally recognised centre of distinction for medical research. It has achieved this recognition by promoting excellence in the conduct and support of its medical research projects. The Institute also portrays the essential features of innovation, risk taking and discovery which excites all who are associated with the organisation QIMR is a statutory body with a tradition that has been developed under the umbrella of the QIMR Act (1945). The Act has been amended many times since it was initially passed by parliament but despite these amendments, it no longer provides an appropriate framework for the operation of a modern medical research institute. Recently, the Minister for Health announced a review of the Act and this has been embraced by the QIMR Council who look forward to working under revised or new legislation.

QIMR is part of the Queensland Government’s Smart State strategy. It is a tangible and successful example of the benefits that may ensue from the bipartisan support that QIMR has received over many years from the Queensland Government. In 2004-2005, QIMR received $5.35 million from the Queensland Government which partly paid for the support services that enabled QIMR’s world-class scientists to successfully compete for $30 million in grants for research into cancer, infectious diseases and other diseases that affect the developed and developing world.

We are very grateful for the support of the Queensland Government. However, their contribution has been static for the past few years whereas the costs of doing medical research have risen dramatically. Now the Queensland Government contribution only covers approximately 50% of the total cost of accommodating QIMR’s research scientists and students. Medical research is expensive and to achieve the breakthroughs that Queenslanders expect, scientists require the latest in equipment, facilities and support. QIMR Council and the QIMR Trust are challenged by our scientists’ needs and recognise the importance of providing world-class facilities, which will underpin their research.

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To that end, QIMR Council and the QIMR Trust have funded the expansion of scientific support services at QIMR at a cost of $11.35 million, which includes the fit out of a floor of the Clive Berghofer Cancer Research Centre. The development will accommodate a new proteomics and glycomics facility and the Institute is most grateful to the Federal Government for funding of $5 million to enable the purchase of state-of-the-art equipment for this facility.

QIMR also recognises the need to convert results into knowledge and experimental therapies that have an impact on the prevention and treatment of disease. In most cases, this is a painstakingly slow and expensive process, but one that is being addressed by ensuring that QIMR has the programs, staff and facilities to translate research results into practical solutions for doctors. Thus QIMR accommodates clean manufacturing and clinical trial facilities that enable the preparation and testing of new experimental therapies.

As the cost of accommodating medical research projects increases, QIMR is increasingly dependent upon the support of people who donate or bequeath to the cause.

The enthusiasm and commitment of QIMR supporters is truly humbling and the Institute will always strive to commit all that is received to the research effort at QIMR. QIMR also acknowledges and thanks the many members of its committees. It is particularly indebted to the members of QIMR’s Council and Trust and would like to particularly acknowledge Dr Paul Bartley (1999-2005), Ms Clare Endicott (2000-2005) and Dr Brandon Wainwright (2000-2005) whose terms have concluded for their participation and commitment to the QIMR Council.

Queensland Institute of Medical Research

Council Members 2004–2005

Sir Bruce Wilson, Dr Gerry FitzGerald, Dr Paul Bartley, Mr Paul Wright, Prof Judith Clements

Sir Bruce Watson AC BE (Elec)BCom Sir Bruce Watson was born in Queensland in 1928. He became General Manager of the Agnew Nickel Mining Joint Venture in Western Australia in 1975. In 1977, he returned to Brisbane as a Director and later as CEO and Chairman of MIM Holdings Limited. Sir Bruce has been a Member of the Supervisory Board of Metallgesellschaft AG, a Director of Boral Limited, ASARCO Inc, National Australia Bank Limited and Chairman of the Gas Corporation of Queensland Limited.

From 1992 to 1995 Sir Bruce served as National President of the Australian Institute of Company Directors and in 1992 as President of the Australasian Institute of Mining and Metallurgy. In June 1985 he was knighted in recognition of his most distinguished service to Queensland industry and in 2004 Sir Bruce was made a Companion of the Order of Australia.

Dr Gerry FitzGerald MD BS BHA FACEM FRACMA FACHSE Dr FitzGerald is the Chief Health Officer for Queensland. He graduated from The University of Queensland in 1976 and after two years at the Mater Hospital, worked as Medical Registrar and subsequently Director of the Emergency Department at Ipswich hospital for over ten years. He joined the Queensland Ambulance Services as Medical Director in 1990 and subsequently became Queensland Institute of Medical Research

Commissioner for almost ten years.

Having held numerous positions within the College for Emergency Medicine and the Journal Emergency Medicine, part of his current position represents the Department of Health on numerous Councils and Boards including the NHMRC and ACHS. Dr Paul Bartley MB BS (Hons) (Qld) MRACP FRACP FACE SIA (Aff) (To 1 June 2005) Dr Bartley is a Clinical Associate Professor of Medicine, University of Queensland, consultant endocrinologist, and Past President of the Australian Diabetes Society (1994-1996). Dr Bartley was also a Councillor of AMAQ (1997-1999) and a USPHS Research Fellow, NIH in 1975-1976).

Mr Paul Wright FAIM FAIBF FAICD Mr Wright is a widely experienced businessman with over 25 years in senior executive corporate roles encompassing the banking, construction, health insurance and hospitality industries. A company director for over 20 years, he has served as President/Chairman of the Australian Institute of Management and the Royal Flying Doctor Service Queensland Division. He is currently Chairman of the Queensland Institute of Medical Research Trust and The CyberInstitute Pty Ltd. His current board appointments include QIMR, RFDS, The CyberInstitute Pty Ltd and PQ Lifestyles Pty Ltd.

Professor Judith Clements BAppSc MAppSc PhD Professor Clements has over 20 years experience as a basic researcher in biomedical research, primarily in the general field of molecular endocrinology. Her current research seeks understanding of the molecular basis of hormone dependent and urogenital cancers such as prostate, breast, ovarian and endometrial carcinoma. She is currently Program Leader of the Hormone-Dependent Cancer Program within the Science Research Centre at the Queensland University of Technology and also an NHMRC Principal Research Fellow.

Professor Brandon Wainwright BSc (Hons) PhD (To 1 June 2005) Professor Wainwright is a Program Leader at the Institute for Molecular Bioscience at The University of Queensland. Recently his laboratory was amongst those which isolated the gene defective in the most common form of cancer, basal cell carcinoma. Professor Wainwright is a Founding Member of the Asia-Pacific International Molecular Biology Network, Chairman of the Grants Committee of the National Health and Medical Research Council of Australia and was awarded the Gottschalk Medal by the Australian Academy of Science in 1998.

Ms Clare Endicott BA LLM (To 1 June 2005) Ms Endicott was admitted as a Solicitor in 1978 and has practised as a litigation lawyer since her admission. She is a partner of

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Prof Brandon Wainwright, Ms Clare Endicott, Prof Lyn Griffiths, Prof Peter Brooks, Mr Paul Fennelly, Prof Bryan Campbell, Prof Alan Lopez, Mr Christopher Coyne

Macrossans Lawyers, Chair of the Solicitors Complaints Tribunal, a Senior Counsellor with the Queensland Law Society, a Director of Guide Dogs for the Blind Association Queensland and a Director of Queensland Rail.

Professor Lyn Griffiths BSc(Hons) PhD Professor Griffiths is Director of the Genomics Research Centre at Griffith University Gold Coast, Head of the GU School of Health Science, and past Director of the Australian Society of Medical Research (ASMR) from 1999 to 2001. She has authored over 90 peer-reviewed publications in molecular genetics international journals, and is Chair of the Scientific Program Committee for the next International Congress of Human Genetics. She was awarded the Centenary Medal for Distinguished Service to Education and Medical Research.

Professor Peter Brooks MD FRACP FRCP Edin FAFRM FAFPHM MD Lund (Hon Causa) Professor Brooks was Foundation Professor of Rheumatology at the University of Sydney prior to becoming Professor of Medicine at St Vincent’s Hospital, Sydney in 1992. He was appointed Executive Dean of Health Sciences at the University of Queensland in 1998, has extensive research experience in basic inflammation and treatment of rheumatic diseases and has been a member of the Fellowships Committee and Partnerships Committee of the NHMRC. 4

Mr Paul Fennelly BA LLB Mr Fennelly is Director-General of the Department of State Development and Innovation and has wide experience in financial management, business and public administration.

Professor Bryan Campbell AM MD BS FRACP FRACMA Professor Campbell was formerly Chief Health Officer and Head of The University of Queensland Medical School. He has been a Councillor of the Royal Australasian College of Physicians, the Royal Australian College of Medical Administrators and a member of the National Health and Medical Research Council. He is currently Deputy Chair of the Australian Health Ethics Committee and a member of the NHMRC Embryo Research Licensing Committee.

Professor Alan Lopez BSc (Hons) MS Phd (From 2 June 2005)

of his research competence and is a member of Australia’s NHMRC Program Grants Committee.

Mr Christopher Coyne LLB (From 2 June 2005) Christopher Coyne is a solicitor practising insurance law, health services, corporate governance and risk management. He was admitted as a solicitor in 1979 and was a partner in the national legal firm Clayton Utz from 19842004. Adjunct Professor at the T.C. Beirne School of Law, he has been a long serving member of the Mater Health Services Human Research Committee, the Queensland Health Research Ethics Committee, the Australian Health Ethics Committee and the NHMRC Gene and Related Therapy Research Advisory Panel.

He is Board Chairman of the Queensland Law Society, Singapore Captive Insurer and is also a Director of the Heart Research Institute (Queensland) and the Makim Pastoral Group.

Professor Lopez is Professor of Medical Statistics and Population Health at the University of Queensland and a consultant to the World Health Organisation. He has published widely on mortality analysis and causes of death, and is co-author of the seminal Global Burden of Disease Study (1996) which has greatly influenced debates about priority setting and resource allocation in health. He has been awarded major research grants in population health in recognition

Queensland Institute of Medical Research

From the Director Professor Michael Good, B Sc(Med) MBBS(Hons) PhD MD DSc

This year QIMR celebrates its Diamond Jubilee. Enacted in 1945, the Queensland Institute of Medical Research Act established an institute dedicated to the betterment of the health and well-being of the people of Queensland. From an original staff of seven, housed in temporary quarters in Victoria Park 60 years ago, QIMR has expanded to occupy two multi-story buildings with scientific and support staff exceeding 700 today in 2005 The Institute’s history is steeped in exceptional people and exceptional research, traditions established early by its Founding Father, Dr Edward Derrick, and Dr Ian Mackerras, first Director. Each year, QIMR contributes to the global bank of medical knowledge and each year, QIMR scientists are recognised and awarded for their discoveries and achievements. The 2004-2005 year is no exception.

Some Research Highlights In the international arena, QIMR scientists in the EBV Biology Laboratory are helping to combat nasopharyngeal carcinoma, a virulent cancer of the nose and throat which over 100,000 people, mainly Chinese and those of Chinese descent, develop each year. An immunotherapy treatment for this cancer is being developed at QIMR, the only centre in Australia to research the disease.

Each year, there are more than 12,000 deaths related to dengue and in Vietnam it is one of the biggest killers of children under the age of five. Mosquito control researchers have enlisted the aid of copepods, microcrustaceans that prey on the dengue-carrying Aedes aegypti mosquito larvae, to completely eliminate the breeding of these mosquitos, and consequently dengue, in 42 Vietnamese communities.

Researchers in the Helminth Biology Laboratory form part of an international research consortium, funded by the Gates Foundation, that has developed and initiated clinical trials for recombinant vaccines to combat infection by the human hookworm, a blood-feeding nematode that infects 740 million people throughout the developing world.

Queensland Institute of Medical Research

Findings from the Clinical Tropical Medicine Laboratory, that a group of HIV drugs known as antiretroviral protease inhibitors may also be effective for treating malaria, hold extremely positive implications for improved health in poorer nations of the world where there are high rates of HIV and malaria co-infection.

Molecular Geneticists have genotyped and mapped the Trichomonas vaginalis genome, a sexually transmitted organism that infects around a billion people worldwide and Molecular Parasitologists have completed successful pilot vaccine trials against canine echinococcosis, which causes hydatid disease in China. In the Molecular Immunology Laboratory, scientists have demonstrated that attenuated infection with an ultra-low dose of parasites can induce immunity to multiple strains of malaria and that cell-mediated immunity appears to be a major component of protection.

Scientists researching women’s cancers discovered that having twins reduces the risk of many types of women’s cancer and that starting a family later in life increases the risk of breast cancer and melanoma, but reduces the risk of ovarian, cervical and uterine cancer.

An Australia-first study to find the causes of the poorly understood endometrial cancer was also initiated during the year.

In the Genetic Epidemiology Laboratory, collaborative research with the Royal Prince Alfred Hospital on the influence of genes on alcohol consumption and dependence revealed that although these two factors are closely related, variation in long-term alcohol intake is almost entirely due to genetic differences, indicating that some people are born with an increased risk of developing alcohol-related 5

From the Director

problems. The laboratory has also identified a major gene for migraine on chromosome 5 and regions for IQ on chromosomes 2 and 6.

In the Cancer and Population Studies Laboratory, evidence has been found that non-steroidal anti-inflammatory drugs reduce the risk of skin cancer and that smoking and obesity greatly increase the effects of acid reflux in the development of Barrett’s oesophagus.

In experimental models, the Immunoregulation Laboratory has shown that IL-4 secretion by tumour cells alters the tumour specific CD8+ T cell response and leads to increased frequencies of secondary tumours. This suggests that production of immunoregulatory hormones is one way that tumour cells can escape elimination by the immune system.

Previous success in treating advanced metastatic melanoma with an autologous dendritic cell-based vaccine in the Cancer Immunotherapy Laboratory has led to a new clinical trial for prostate cancer with Dr Frank Gardiner from The University of Queensland, and the Northern section of the Urological Society of Australia.

Other clinical trials currently underway or being planned include immunotherapeutic treatments for human cytomegalovirus, glioma and early stage melanoma.

Two new laboratories were welcomed into the Institute during the year. Dr Qin Cheng, a longterm collaborator in the Infectious Diseases and Immunology Division, now heads the Malaria Drug Resistance and Chemotherapy laboratory, based at the Army

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Malaria Institute at Enogerra. In October 2004, Professor Sunil Lakhani took up an appointment with The University of Queensland and is now head of the Molecular Pathology Laboratory at QIMR. The Population Studies and Human Genetics Division also welcomed Professor Peter Visscher into its ranks this year, an internationally renowned quantitative geneticist from the University of Edinburgh.

Awards and Achievements In June 2005, Dr Geoff Hill, head of the Bone Marrow Transplantation Laboratory, was named Queenslander of the Year for advances in his field that may significantly improve patient survival after transplantation. His research may ultimately lead to improvements in cure rates by limiting lifethreatening transplant complications whilst enhancing the eradication of leukaemia during the transplant procedure.

Professor Brian Kay became a Member of the Order of Australia (AM) in the Queen’s Birthday Honours List for service to medical science and public health, particularly through research into the control and elimination of mosquitoborne arbovirus diseases in northern Australia and Asia.

In May 2005, Daniel Wallace won the Queensland Premier’s Award for Medical Research in the Senior Postdoc category for novel research into both anaemia and haemochromatosis – two seemingly opposite conditions in which the same hormone, hepcidin, may hold the key. Kathy Andrews was a finalist for the same Award.

The Derrick-Mackerras Memorial Lecture represents a highlight in QIMR’s academic year. This year, the lecture was presented by Dr James Watson, Chief Executive of Genesis Research and Development Corporation. In his lecture entitled B2B – From Bone to B Cells, Dr Watson outlined a new pathway that influenced both B cell and bone development and discussed the implications for new therapeutics to treat disorders such as lupus and osteoporosis.

The Institute’s high achievement awards were presented to QIMR staff and supporters following the lecture.

Professor Nick Martin, head of Genetic Epidemiology, won the 2004 Ralph Doherty Prize for Excellence and Leadership in Medical Research.

The Institute was delighted to make Mr Peter Wills a QIMR Fellow, and to award a Bancroft Medal to Ms Sue Cassidy for her outstanding support to researchers as Animal House Manager. Long Service Awards were presented to two scientists who have given over 25 years service to the Institute, Dr Greg Lawrence and Dr Ihor Misko, both of whom joined the Institute in 1978.

The Indigenous Program celebrated its third anniversary with a Seminar in June 2005. Mr Michael Gooda, CEO for the CRC for Aboriginal Health, gave an enlightening address sharing his insights on contradictions, confusion and ironies in Aboriginal affairs. QIMR is committed to improving Indigenous health through research and this year attracted a new Honours student Simõne Smith and the Program’s first cadet, Lisa Whop. A new Project Officer, Vanessa Clements was

Queensland Institute of Medical Research

also engaged during the year, in a position funded by the Australian Centre for International and Tropical Health and Nutrition.

cancer seminars in all the major centres along the route and the event raised significant funds for skin cancer research.

Grants and Funding Success NHMRC grants awarded during the 2004-2005 year included eight new project and two program grants, bringing total NHMRC funding to over $17 million in total. For the same period, Institute scientists received three Research Fellowships, three Career Development Awards, five training fellowships and five postgraduate scholarships.

The Development Department also performs important functions in providing guided tours of the Institute and organising speakers for external engagements which promote QIMR’s research to the community. During this year, more than 8,000 people learned about the Institute’s work through these tours and engagements. The Department also publishes a quarterly newsletter Life Lab, which features our latest research. It has a circulation of 22,000.

Two NIH grants, totalling over $4 million, were received from the United States, one to develop a global Group A Streptococcus vaccine based on the M-protein, and the other to further explore the genetic epidemiology of alcoholism and comorbidity. Total competitive grants received for the year were almost $31 m.

Eight grants were received from the Queensland Cancer Fund during the year to cover a range of different cancer research areas and the Leukaemia Foundation continues to provide significant funding for the Leukaemia Foundation laboratory headed by Dr Professor Andrew Boyd from The University of Queensland.

The Institute is extremely grateful for the continuing support of Atlantic Philanthropies, Mr Clive Berghofer and the very many other donors, both large and small, whose generous contributions to QIMR progress the cause of medical research in Queensland by no small measure.

QIMR also benefits from other sources, and in December 2004, the Development Department negotiated a sponsorship contract with Suncorp to combat skin cancer in Queensland. Suncorp organised a fund-raising Ride for Research in June 2005 in which over 100 cyclists rode from Rockhampton to Brisbane over seven days, with much publicity. QIMR speakers gave skin

Queensland Institute of Medical Research

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Xxxxxxxx

A celebration of 60 years

The First Laboratory In the mid 1930s, the Queensland Department of Health established a Laboratory of Microbiology and Pathology, headed by Dr Edward Derrick, with the task of creating a quality forensic pathology service for Queensland. Early discoveries in this laboratory included collaborative work with virologist Dr Macfarlane Burnet from the Walter and Eliza Hall Institute which identified Q Fever, new forms of leptospirosis, and native animals as carriers of various diseases.

War Triggers Change During World War II, the laboratory’s research activities virtually ceased with the loss of staff into the armed forces and a heavy routine workload. This compelled Derrick to include in his 1944 Annual Report to the Minister of Health that an independent research facility was crucial to solving the state’s disease problems, and should be included in post-war plans for the Queensland.

State Cabinet set up a committee chaired by Derrick to consider the proposal and the outcome of their report was the Queensland Institute of Medical Research Act of 1945.

From top: Dr Edward Derrick, The Laboratory of Microbiology and Pathology, Drs Ian and Josephine Mackerras and Shed 8 – QIMR’s first accommodation

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Leading and Housing the New Institute Dr Ian Murray Mackerras, with extensive experience in malaria control for the Australian Army in New Guinea, was appointed Director on 13 March 1947. Derrick elected to serve as Deputy Director instead so he could continue running the Laboratory of Microbiology and Pathology whilst setting up QIMR to officially commence operations in 1947.

Dr Josephine Mackerras, granddaughter of esteemed

Queensland scientist and physician, Dr Joseph Bancroft, was appointed Senior Parasitologist in 1947. QIMR’s first accommodation was Shed 8, a building in Victoria Park, originally a temporary supply headquarters for the US Army but one which housed the Institute for 30 years.

The Innisfail Field Station The fevers of north Queensland were a research target stipulated in the QIMR Act, and from 1951 to 1965, a QIMR Field Station based at Innisfail Hospital investigated outbreaks of leptospirosis, scrub typhus, dengue and other tropical fevers. In 1954, an outbreak of dengue fever in north Queensland heightened the need for knowledge of arboviral diseases and as a result, QIMR researchers carried out extensive surveys of mosquito type and distribution across the state during the 1960’s.

Native Animal Vectors Scientists also studied native animals for rickettsia and other viruses, finding Toxoplasma gondii in Queensland rodents and small marsupials, the murine leukaemia virus in a mouse caught in Derrick’s pantry, and also discovered rodents carried strains of brucellosis. An enterovirus epidemic in 1961-1962 prompted collaborative studies with the Commonwealth Serum Laboratories.

A Change of Leadership When Ian and Josephine Mackerras retired in 1961, Derrick finally assumed Directorship of the Institute until his own retirement in 1966 when Professor Ralph Doherty was appointed in his place. Having started at QIMR in 1953, Doherty had risen to the position via successive appointments as Senior Epidemiologist and Deputy Director.

Queensland Institute of Medical Research

He discovered the Ross River virus which caused epidemic polyarthritis and was responsible for QIMR’s first outreach into southeast Asia.

Research Expands into New Areas Throughout the next decade, the Institute’s high standard of research continued and expanded into other areas including asthma and longitudinal studies in birth, growth and death trends in the north Queensland Aboriginal population.

An Oncology section was formed to address the emerging field of tumour viruses with early success in establishing cancer cell lines, two from Burkitt’s lymphoma patients in PNG in which the Epstein-Barr virus was detected, and others in leukaemia. Research into melanoma began in 1970.

Change of Address and Director In 1977, QIMR relocated to new laboratories in the grounds of the Royal Brisbane Hospital. The following year, the Institute also had a new Director, Professor Chev Kidson, who had been Foundation Professor of Medical Biochemistry at The University of Queensland and whose vision for QIMR committed the Institute to a global contribution to medical research with a new focus on major world disease problems.

An Exciting New Era of Research Initiatives during this time included a 5 year malaria vaccine project funded by NHMRC, a major factor in the internationalisation of QIMR, placing it at the forefront globally in the use of monoclonal antibody technology in parasitology. In 1979 a Joint Experimental Oncology Program began with the University of Queensland and the Queensland Cancer Fund as partners. Professor Kay Ellem was appointed as Senior Queensland Institute of Medical Research

Research Fellow in 1980 to become Deputy Director in 1985 and Acting Director from 1989 to 1990. His interests lay in DNA function and metabolism and the regulation of cell growth and differentiation in various cell states including malignancy.

New Partners, New Programs In late 1985 a federal review of research and education requirements for public and tropical health in Australia prompted the establishment of a Public Health Education and Research Program.

Nine centres participated including QIMR, with the outcome of 5 new research programs established as joint initiatives of QIMR and The University of Queensland.

These were: Tropical Health, Experimental Oncology, Liver Research, Transplantation Biology and Experimental Haematology.

Epidemiology was introduced as a discipline into QIMR during the 1980s, particularly through the methodology of twin studies. Work on the Epstein-Barr Virus began in 1989 and by 1993, this was the principal focus in four QIMR laboratories.

External Funding Promotes Expansion With further expansion only possible through additional funding, Kidson inspired researchers to seek external grants from a range of national and international sources, with such success that QIMR won the Top State Business Achievement Award in 1990 for its contribution to Queensland’s economic development. Added to the administrative independence it had already won in March 1988 when amendments to the QIMR Act converted the Institute to a statutory

From top: QIMR Innisfail Field Station at Innisfail Hospital, Professor Ralph Doherty, QIMR building at Bramston Terrace and Professor Chev Kidson

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A celebration of 60 years

authority, QIMR became highly competitive with other academic institutions in attracting world-class researchers to its laboratories.

The Bancroft Centre Kidson’s final legacy to QIMR was to lobby state government to invest in a new building to house staff numbers which had grown from 50 to 200 under his Directorship. $30 million was committed in the 1988 budget and construction on an eleven storey facility adjacent to the Royal Brisbane Hospital began in 1989. The building was officially opened in 1991 and named The Bancroft Centre as a memorial to the family with whose history QIMR is inextricably linked.

An Era of Collaboration and Partnerships Professor Lawrie Powell became fifth Director of QIMR in 1990 and led the Institute strategically into an era of collaborative and translational research. The proximity of QIMR to the Royal Brisbane Hospital promoted interactions between researchers and clinicians and provided ready access to the Queensland Radium Institute, the Bone Marrow Transplantation Unit, hospital wards, operating theatres and out-patient clinics for the establishment of clinical trials.

From top: , Members of the Joint Oncology Experimental Program, Members of the Tropical Health Program, The Bancroft Centre and Professor Lawrie Powell, fifth Director of QIMR

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A partnership with The University of Queensland established a new Transplantation Biology Program, combining expertise in basic immunology with surgical skills to study immune tolerance and the cellular mechanisms involved in graft rejection. QIMR research into nutrition became internationally recognised for shifting clinical assessment into the laboratory to result in a substantial improvement

in liver transplantation outcomes for children.

In 1993, the Institute was appointed coordinating partner for the Cooperative Research Centre (CRC) for Vaccine Technology, with QIMR scientist Professor Michael Good as Director. It was also a supporting organisation during the setting up of the CRC for Diagnostic Technologies in 1995 and a major partner in the CRC for Human Gene Discovery and the CRC for Aboriginal Health, both of which started work in 1997. The Australian Centre for International and Tropical Health and Nutrition was established in 1995 as a joint venture of The University of Queensland and QIMR with affiliation to the Australian Army Malaria Institute.

Communicating with the World With the new conference and seminar facilities in the Bancroft Centre, QIMR became a centre for discussion and dissemination of research, attracting renowned national and international speakers in the medical field. Successful international symposia promoted important interactions and the number of visiting international scientists spending extended periods in QIMR laboratories increased markedly. The Derrick Mackerras Memorial Lecture was established as an Institute tradition in 1991.

A Public Relations and Development Department was established in 1994 to increase the awareness and heighten the profile of QIMR amongst community and corporate sectors and to raise vital funds for ongoing research. In 1997, funds of $60 million dollars were made available to QIMR for the construction and operation of a comprehensive Queensland Institute of Medical Research

cancer research centre unparalleled in Australian History. $20 million came from an anonymous donor and a further $20 million each from both the Queensland and Federal Governments.

By the end of the 20th Century, QIMR staff numbers had reached 440 with an annual budget that had trebled in just 9 years. Two independent scientific reviews had highly commended the Institute which had also received prestigious Block Funding by the NHMRC. With the new Cancer Centre about to allow for a significant increase in staff numbers, QIMR stood at the threshold of the new millennium in a position to contribute substantially to the new biotechnology and knowledge-based industry being fostered in Queensland.

The New Millenium The year 2000 saw the retirement of Professor Powell after 10 years and the Directorship assumed

by Professor Michael Good, with Professor Adèle Green as Deputy Director.

The Clive Berghofer Cancer Research Centre The new CBCRC building was officially opened in August 2001 by the Queensland Premier, the Honourable Mr Peter Beattie MP and the Federal Minister for Health and Aged Care, the Honourable Dr Michael Wooldridge MP. The new building enabled QIMR to perform early stage clinical trials alongside molecular biology and epidemiological research, thus greatly accelerating the development of new therapeutics and vaccines.

Queensland Institute of Medical Research

Commercialisation and the Business of Biotechnology A Business Development Executive was appointed in 2001 to lead the Institute’s commercial agenda by identifying and protecting the intellectual property generated

by QIMR research and actively seeking partners and/or funding for commercialisation of its discoveries.

A facility to produce clinical material to a GMP standard for clinical trials of cell-based therapeutics began manufacture in 2002. In the same year, Q-Pharm Pty Ltd, a joint venture between QIMR, The University of Queensland and Professors Hooper and Dickenson, became operational as a Phase 1 Clinical Trials Facility to test potential new therapeutic products on humans.

Indigenous Health An Indigenous Health Research Program began operations in 2002 with the goal of finding ways to improve the health and well-being of Aboriginal and Torres Strait Islander peoples. The program has built collaborative projects with the cancer and populations studies, malaria and scabies, molecular genetics, molecular immunology and bacterial pathogenesis laboratories.

Now, in 2005, QIMR celebrates it’s 60th year with pride and looks forward to continuing its proven tradition of achievement in cutting edge medical science for another 60 years.

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Research

Research at QIMR takes place in 40 different laboratories under four separate Divisions, each with a major focus. A number of important research collaborations within and between the laboratories take place, as well as with external entities

The Infectious Diseases and Immunology Division focuses on improved understanding of viruses, bacteria and parasites, and how they interact with the immune system with the aim of developing new tools to diagnose, treat and prevent infection.

The Cancer and Cell Biology Division integrates research on the cellular, molecular and genetic basis of a wide range of cancers, including melanoma, leukaemia, breast, ovarian, endometrial and colorectal cancer to develop screening tools for early detection and devise strategies for the treatment and prevention of cancer.

The Population Studies and Human Genetics Division utilises a wide range of contemporary epidemiological, genetic and molecular techniques to investigate a spectrum of diseases relevant to the Australian population aimed at understanding the mechanisms of disease and identifying potential therapeutic targets. This Division includes the Indigenous Health Research Program which carries out collaborative research projects for the improvement of the health and well-being of Aboriginal and Torres Strait Islander peoples.

The Therapeutic Development and Clinical Research Division develops and tests immunotherapeutics manufactured within the Q-Gen laboratory at QIMR. Currently, it oversees clinical trials using cell-based therapeutics that target post-transplant lymphoma, malignant melanoma, prostate cancer and cytomegalovirus infection.

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Queensland Institute of Medical Research

Infectious Diseases and Immunology Division Chair – Associate Professor James McCarthy – Joint appointment with Royal Brisbane and Women’s Hospital

The focus of the Infectious Diseases and Immunology Division is improved understanding of viruses, bacteria and parasites and how they interact with the immune system. Through such increase in knowledge, it will then be possible to develop: • new tools to diagnose infection • new treatments for infection • new vaccines to prevent infection Work undertaken by the Division ranges from detailed studies of how the immune system operates, including how it responds to challenge by a variety of infectious agents, to study of the biology of a number of pathogens ranging from viruses to worms – to the development and testing of vaccines.

Highlights of this year have included the appointment of longstanding collaborator, Dr Qin Cheng from the Army Malaria Institute, Enoggera QLD as a Lab Head, awards to Dr Geoff Hill of Queenslander of the Year, and to Professor Brian Kay of an AM for his work in mosquito control. Brian was also a key partner in one of two successful applications to the Gates Foundation from the Division for work on Infectious diseases, the other going to Alex Loukas. Michael Good’s Molecular Immunology laboratory received a significant International Grant from the NIH for vaccine-related research on Group A streptococcus.

Bacterial Pathogenesis Bone Marrow Transplantation Cellular Immunology Clinical Tropical Medicine EBV Biology EBV Immunology EBV Molecular Biology Helminth Biology HIV Molecular Virology Immunology and Infection Immunoregulation Immunovirology Malaria and Scabies Malaria Biology Malaria Drug Resistance and Chemotherapy Molecular Genetics Molecular Immunology Molecular Parasitology Mosquito Control Tumor Immunology

Queensland Institute of Medical Research

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Infectious Diseases and Immunology Division

Bacterial Pathogenesis Associate Professor Kadaba Sriprakash David McMillan , Michael Binks , Catherine Denham Josephine Shera, Mark Davies , Melina Georgousakis Karen Taylor, Thanh Tran

This laboratory investigates how Group A streptococcus (GAS) is able to overcome host defense and cause disease. Research is undertaken on characterising novel GAS vaccine antigens, and on the role and extent of horizontal gene transfers between different streptococcal species and how this can turn normally harmless commensal bacteria into potential disease causing bacteria

Biofilms are communities of bacteria that grow together for their mutual benefit. The bacteria in biofilms have different properties to individual free living bacteria. Group A streptococci also form biofilms, and this is probably their natural state during a throat infection. Researching how GAS behave in Biofilms gives a greater understanding of how they cause disease

Highlights Found that Group G streptococcus acquires group A streptococcal genes frequently among populations in whom GAS diseases are endemic Discovered that many different sub-types of GAS are circulating in Northern India, similar to observations seen in Indigenous Australians living in the Northern Territory of Australia

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Research towards effective vaccine against GAS infection Recent work confirmed the high diversity of circulating types in the northwest part of India, similar to isolates from Australia. However, the composition of the types may differ in these two countries, thus any vaccine based on the highly variable antigen would have to be specifically tailored for the region where it is targeted. The search for other vaccine antigens that will provide broad spectum protection continues. It has been suggested streptococcal adhesins such as SfbI can offer protection against GAS infection but the laboratory has now shown that although mucosal antibodies to this protein prevents GAS adherence, it does not elicit opsonic antibodies and does not prevent systemic bacterial growth and dissemination to internal organs after subcutaneous GAS challenge.

Are commensal streptococci in bad company among pathogenic relatives?

Human group G streptococci are largely commensal streptococci.

Horizontal genetic transfers between this organism and pathogenic GAS have already been observed.

Researchers in this laboratory recently confirmed the ongoing nature of phage-mediated lateral

acquisitions between these species, and that this occurs at an appreciable frequency. The significance of this finding for streptococcal epidemiology and in effective control of streptococcal diseases is far reaching, particularly in GAS-endemic regions.

Fibronectin binding and GAS adherence GAS expresses a large number of fibronectin binding proteins which promote adherence to host cells. While fibronectin binding is important in adherence, the first event in the process of colonisation, it has now been shown that the extent of fibronectin binding is not a critical determinant of adherence. A collaborative study on phylogenetic analysis of two subtypes of PrtF2, another fibronectin binding adhesin, revealed that one subtype is more variable than the other.

GAS and host innate immunity Some GAS strains express Streptococcal Inhibitor of Complement (SIC). SIC is a multifunctional protein with distinct structural domains. Molecular dissection of SIC to determine association between its structural and functional domains was undertaken in a collaborative study.

Queensland Institute of Medical Research

Bone Marrow Transplantation Dr Geoff Hill Kelli MacDonald, Tatjana Banovic, Angela Burman Edward Morris, Vanessa Rowe, Rachel Kuns Alistair Don, Naomi Odorico, Patrick Bunn

The BMT Laboratory works towards understanding the pathophysiology of the complications of bone marrow transplantation (BMT), particularly graft-versus-host disease, with the ultimate aim of developing more effective preventative and treatment therapeutics for translation to the clinical setting Allogeneic stem cell transplantation (SCT) remains the curative treatment of choice for the majority of haematological malignancies but is limited by its serious complications, notably graft-versus-host disease (GVHD). The mobilisation of stem cells by cytokines such as G-CSF has become standard therapy in haematology practise for the purpose of transplantation and has largely replaced bone marrow as a stem cell source. Allogeneic SCT has improved patient outcome

relative to traditional bone marrow transplantation. This laboratory has previously determined that G-CSF alters the ability of donor T cells to induce GvHD, although the mechanisms remain unclear.

GM cells - isolated from ProGP-1 treated mice protect transplant recipients from graft-versus-host disease

In the last year the way in which these growth factors influence NKT cells and leukaemia clearance after transplantation has been identified and these findings are now the basis of a clinical trial at The Royal Brisbane Hospital.

Highlights Defined new cytokines to mobilise stem cells for allogeneic transplantation that are superior to G-CSF for the prevention of GvHD Defined the role of new subsets of cells called NKT cells that help eliminate leukaemia after transplantation Linked improvements in leukaemia free survival to the intensity of G-CSF signalling during stem cell mobilisation Understood the effect of transforming growth factor-beta on transplant outcome Characterised the lineage of dendritic cells and their relationship to macrophages

Queensland Institute of Medical Research

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Infectious Diseases and Immunology Division

Cellular Immunology Dr Scott Burrows John Miles, Jacqueline Burrows , Sharon Silins, Kate Green, Melissa Bell

The main focus of the Cellular Immunology Laboratory is the cytotoxic T lymphocyte (CTL) and factors controlling its primary function in killing virus-infected cells, foreign transplanted cells and tumour cells

The immunogenicity of a viral cytotoxic T cell epitope is controlled by its MHC-bound conformation.

A. Immunogenic peptide conformation (side view) B. Non-immunogenic peptide conformation (side view) C. Blue: Immunogenic conformation Green: Non-immunogenic conformation (top view)

Highlights Discovered that large clonal expansions of virus-specific T cells can dominate in the peripheral circulation for at least 18 years Found that the strength of a cytotoxic T cell response can be influenced by the conformation of the target MHCbound peptide Discovered that unusually long cytotoxic T cell epitopes are recognised by a highly restricted repertoire of T cell receptors Found that T cell receptors can bind MHC-class-I-bound peptides by adopting an orthogonal binding mode

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Mammalian cells have developed complex mechanisms to alert the body’s immune defence mechanisms to virus infection. After a virus enters a cell, short peptide epitopes of viral origin are processed by the infected cell and presented on the cell surface to flag a population of white blood cells called CTLs to kill the virusinfected cells.

of a foreign peptide, when presented on the surface of an infected cell, can have a major impact on whether T cells are raised against the peptide, as illustrated at left. These data indicate that the immunogenicity of an antigenic peptide is influenced, not only by how well the peptide binds to MHC molecules, but also its bound conformation.

This year, the Cellular Immunology laboratory has conducted studies to determine how long individual antiviral T cell clonal expansions survive in the blood, and made the surprising discovery that a single T cell clone can play a major role in controlling a persistent viral infection for at least 18 years of a person’s life. This study provided an important advance in understanding the longevity and stability of the T cell repertoire towards a persistent pathogen.

Many thousands of potentially antigenic peptides are encoded by an infecting pathogen, however only a small proportion induce measurable T cell responses. A variety of factors can influence the strength of the T cell response to a foreign peptide. Another project conducted this year has revealed that minor changes in the conformation Queensland Institute of Medical Research

Clinical Tropical Medicine Associate Professor James McCarthy – Joint appointment with Royal Brisbane and Women’s Hospital Cielo Pasay, Kathy Andrews, Alex Sykes, Yvonne Adams, Nelson Lee, June Chia, Petrina Hilton, Lewis Melville, Ranbir Sarai

The Clinical Tropical Medicine Laboratory investigates how malaria and other parasites cause disease, and on developing new and improved tests both to diagnose these parasite infections, and to detect drug resistance The discovery that a number of antiretroviral protease inhibitors (ARPI) already in use for treating HIV infection show activity against the malaria parasite has led to further in vitro work and to studies in a rodent model of malaria.

Drug resistance in human scabies is a growing threat to community-based control programs currently underway in Indigenous communities across northern Australia. A joint project with Dr Shelley Walton and others from the Menzies School of Health Research to discover the mechanisms of drug resistance in human scabies has developed a genotyping test that may assist in detecting drug resistance in this condition.

In collaboration with Dr Andrew Kotze from CSIRO and Dr Moses Bockarie from the PNG Institute for Medical Research, further progress has been made in studies of drug resistance in human intestinal worms. Molecular and in vitro diagnostic tests for detection of drug resistance have been developed and applied in the field, and a third annual field study was carried out in Madang Province, PNG in November 2004. This work is supported by a Grant from the World Health Organisation (TDR).

Queensland Institute of Medical Research

Also funded by the World Health Organisation is a collaborative study with Dr Qin Cheng of the Australian Army Malaria Institute, which explores why so-called rapid diagnostic tests for malaria sometimes do not work. This has led to the identification of significant polymorphism in the HRP-II protein which is now the target of rapid diagnostic tests, as it may help explain why the tests are sometimes unreliable. Studies to identify the epitopes recognised by the antibodies used in these tests are underway.

Following an outbreak of severe infections due to a drug-resistant strain of Staphylococcal aureus in a southeast Queensland Indigenous community, a project has been undertaken to investigate the epidemiology of this important pathogen. This work is in collaboration with investigators at the Indigenous Health Unit at the School for Population Health, UQ, the CRC for Diagnostics at QUT, and is funded in part by Queensland Health.

Drug resistance of human intestinal worms is the subject of a PNG study in collaboration with CSIRO and the PNG Institute of Medical Research

Highlights Found that clinically used antiretroviral protease inhibitors, such as ritonavir-lopinavir, saquinavir and atazanavir, inhibit the in vitro growth of P. falciparum at or below concentrations found in human plasma after oral drug administration Identified a cellulose sulphate derivative (CS10) with potential as an anti-adhesive agent targeting the major receptor associated with pregnancy malaria Found that adherence of P. falciparum-infected erythrocytes to novel receptor on CHO-745 cells is inhibited by protein A in the presence of human serum Further field testing undertaken in PNG of an in vitro test to measure how sensitive intestinal worms are to antiparasitic drugs Identified immunogenic antigens with the potential for diagnosis of strongyloidiasis

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Infectious Diseases and Immunology Division

EBV Biology Professor Denis Moss Joanne Davis, Jai Kumar Duraiswamy, David Tscharke Monica Corban, Leanne Morrison, Lea Heslop Angela Neering, Mark Smith

The EBV Biology Laboratory is committed to understanding the biology and immunology of two clinically important human pathogens, Epstein-Barr virus (EBV) and vaccinia virus (VACV) with the ultimate aim of capturing laboratory findings and using them in human clinical trials

Highlights Mapped the parts of vaccinia virus (VACV) that are recognised by CD8+ T cells in mice and demonstrated that route of immunisation can affect the parts of a vaccine to which the majority of an immune response is generated Attempted to determine the parts of VACV that are recognised by CD8+ T cells in vaccinated people and showed that responses are broad, with a large number of virus proteins being targeted Initiated clinical trial on adoptive transfer of EBV-specific T cells as a treatment option for nasopharyngeal carcinoma Gained an understanding of the protective capacity of a polyepitope vaccine formulation delivered in adenovirus to protect against growth of human nasopharyngeal carcinoma (NPC)

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Evaluating a formulation designed to control nasopharyngeal carcinoma (NPC) The laboratory is testing the protective capacity of a vaccine formulation that consists of a series of minimal EBV-specific CTL epitopes encoded in a replicationdeficient form of adenovirus. Results show that this formulation can protect immunocompromised mice in which human nasopharyngeal carcinoma (NPC) cells are growing, as illustrated at left.

A peptide-based protocol for activating an immune response in human cells suitable for adoptive transfer Conditions required to stimulate components of the EBV-specific cytotoxic T cell response that will be used in adoptive transfer into patients with end-stage have been defined.

The protocol involves the use of defined peptides bound to an EBVtransformed cell of the patients under defined conditions.

Mapping immune responses to vaccinia virus (VACV) Collaborative projects to map and characterise the CD8+ T cell responses to vaccinia virus VACV in humans and mice have been undertaken this year. This work

is important for understanding VACV as a vaccine vector and also for understanding immunity to poxviruses such as monkeypox and smallpox, the emergence or re-emergence of which is a current cause for concern.

A major achievement during the year has been mapping of the CD8+ T cell epitopes of VACV in mice, and using this new information to show that the route of vaccination can affect the parts of a virus or vaccine to which the immune system directs its response. These findings were published in the prestigious Journal of Experimental Medicine in January 2005.

Above left: Human NPC tumour cells growing in immunocompromised mice before and after adoptive transfer of immune cells activated with the NPC vaccine formulation: left – human NPC growing in mice, and right: mice cured of NPC with vaccine formulation

Queensland Institute of Medical Research

EBV Immunology Dr Ihor Misko

Simone Cross, Kate Green

The memory response to EBV involves killer T cells that possess antiviral and anti-self capabilities. The priority is to discover how these cross-reactive immune cells discriminate self and viral signals in generating protective immunity without inciting harmful autoimmunity Over several years, this laboratory has built a robust human model system to probe the regulatory mechanisms that maintain peripheral self tolerance without compromising T cell responses against pathogens.

This model is based on an earlier ďŹ nding that auto-reactive cytotoxic T cells can be induced in culture by molecular mimicry involving crossreactive T cells that corecognise closely homologous self and viral peptides.

The stage has now been reached in these research endeavours where cross-reactive memory T cells can readily be manipulated in culture so that they still respond to viral peptide but no longer respond to self peptides. This split molecular mimicry model provides an exciting opportunity to identify novel biomarkers associated with self-tolerance, autoimmunity and antiviral immunity.

So far, the search for these biomarkers has predominantly targeted signalling proteins associated with T cell receptor activation and proteins involved in the lytic machinery of cytolytic T cells. Interesting differences have been found between memory T cells Queensland Institute of Medical Research

reactivated by normal means or by simple manipulation to justify a fullscale search for candidate genes and proteins involved in split molecular mimicry. Outcomes from this approach will result in the design of novel strategies to deactivate harmful T cell behaviour in autoimmune disease or bolster T cell responses to overcome tolerance resistance in tumour regression.

Antiviral CD8 T cells coexpress granzyme A, granzyme B and perforin proteins

Highlights Discovered a novel procedure to switch off auto-reactivity in crossreactive T cells without affecting the response to pathogen Demonstrated that activated antiviral T cells express abundant transcripts for recombination activating gene (RAG)1 and RAG2, suggesting that T cell receptor revision may occur in the periphery

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Infectious Diseases and Immunology Division

EBV Molecular Biology Dr Tom Sculley Kenia Krauer, Marion Buck, Anita Burgess Kingsley Broad, Jenny Pozo Molina, Sofie Lindgren

The Epstein-Barr virus (EBV) is a herpes virus that is the causative agent of infectious mononucleosis and is also associated with several human malignancies. The major area of research in this laboratory involves the study of how the virus is able to transform normal cells into cancer cells

Cellular localisation of the Sin1 protein showing that it colocalises with JNK

Highlights Completed definition of nuclear targeting sequences in the EBNA3B protein

The Epstein-Barr virus nuclear antigen (EBNA) 3B is a hydrophilic, proline rich, charged protein which is thought to be involved in transcriptional regulation of both viral and cellular genes. EBNA3B is targeted exclusively to the cell nucleus and studies have shown that it localises to discrete subnuclear granules within the nucleus.

Colocalisation studies utilising a fusion protein between enhanced green fluorescent protein (EGFP) and EBNA3B with FLAG-tagged EBNA3A and EBNA3C proteins demonstrated that EBNA3B colocalised with both EBNA3A and EBNA3C in the nucleus of cells.

Computer analyses identified four potential nuclear localisation signals (NLS) in the EBNA3B amino acid sequence. Utilising fusion proteins between EGFP and deletion constructs of EBNA3B, and also site-directed mutagenesis, three of the four NLS (aa160-166; aa430434; aa867-873) were shown to be functional, while an additional NLS (aa243-246) was identified within the N-terminal region of EBNA3B.

length human Sin1 protein and a Cterminally truncated isoform, Sin1α, which is produced by alternative splicing. Immunoblot analysis using an anti-Sin1 polyclonal antibody showed that full-length Sin1 and several smaller isoforms are widely expressed. Sin1 was demonstrated to bind to c-Jun N-terminal kinase (JNK) in vitro and in vivo, while no interaction with p38- or ERK1/2family MAPKs was observed. The Sin1α isoform also could also form a complex with JNK in vivo. Despite localising in distinct compartments within the cell, both Sin1 and Sin1α, colocalised with JNK, suggesting that the Sin1 proteins could recruit JNK. Over-expression of full-length Sin1 inhibited the activation of JNK

by UV-C in DG75 cells, as well as basal JNK-activity in HEK293 cells.

These data suggest that the human Sin1 proteins may act as scaffold molecules in the regulation of signalling by JNK.

Characterised the Human Sin1 Gene Showed that the Human Sin1 Gene encodes a JNK-binding Protein

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This laboratory also has an interest in the human Sin1 protein and has investigated the function of the fullQueensland Institute of Medical Research

Helminth Biology Dr Alex Loukas Michael Smout, Tegan Don, Mai Tran Mark Pearson, Cindy Chang, Clea Perkins

The Helminth Laboratory studies the molecular interactions between blood-feeding helminth parasites and their vertebrate hosts, and seeks avenues for exploiting this information to develop vaccines against these parasites In the past 12 months significant progress has been made in the development of recombinant vaccines for the two most important helminth parasites of humans – schistosomes and hookworms.

schistosomiasis. The most promising of these antigens is the tetraspanin, TSP-2. This vaccine reduces worm burdens and liver egg counts by 6570% and holds great promise as a schistosomiasis vaccine.

A recombinant vaccine against hookworm disease has been developed using a canine model to develop and test the efficacy of an aspartic haemoglobinase vaccine against the dog hookworm, Ancylostoma caninum. The vaccine causes significant reductions in adult worm burdens and egg counts in vaccinated animals.

Antibodies against the recombinant haemoglobinase inhibit bloodfeeding, depriving hookworms of nutrients required for growth and reproduction.

Funding has recently been obtained for a new project exploring the secretome of the carcinogenic liver fluke, Opisthorchis viverrini, a parasite endemic throughout SE Asia where it is a major cause of liver cancer (cholangiocarcinoma).

Secretions of the parasite cause cells to hyperproliferate with unchecked DNA damage, providing a likely mechanism by which this helminth causes cancer. The mitogenic secretions from O. viverrini are being identified and the molecular pathways associated with cancer development characterised.

Families of receptors on the surface of the intravascular schistosome blood flukes have been identified using a novel signal sequence trap methodology. Families of fourtransmembrane (tetraspanins) and seven-transmembrane proteins have been identified from the tegument, the outermost layer of the parasite that is in direct contact with host blood. Three of these proteins provide varying levels of vaccine efficacy in a murine model of Queensland Institute of Medical Research

Above: Crystal structure of the hookworm vaccine antigen, Na-ASP-2 Below: Section through a hookworm in situ in a dog intestine. Note the ingested plug of intestinal tissue in the buccal capsule of the parasite

Highlights Developed and initiated clinical trials for recombinant hookworm vaccines Developed novel, efficacious recombinant vaccines against schistosomiasis Identified genes associated with the transition to parasitism in parasitic nematodes

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Infectious Diseases and Immunology Division

HIV Molecular Virology Dr David Harrich Ann Apolloni, David Warrilow, Luke Meredith, Nicole Willemsen, Tracey Bodetti, Cherie Harrich

The focus of the HIV Molecular Virology Laboratory is the discovery of key viral or cellular molecules required for HIV to grow, and to target their action so that HIV growth can be effectively blocked

Above: The HIV-1 Tat protein can enhance RT activity in vitro. The relative in vitro activity of HIV-1 reverse transcriptase is increased in the presence of Tat Below: Acute lymphocytic leukaemia cells with a multivesicular body containing virus-like particles shown by the arrow. Electron-micrograph image (x10,000)

Highlights Demonstrated for the first time that Tat acts directly during HIV-1 reverse transcription Found that Protein kinase C plays an early role during HIV-1 infection

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This laboratory studies the HIV-1 life cycle focusing on entry into human cells and the process of reverse transcription. Reverse transcription is the process by which the HIV-1 RNA genome is converted into a double strand of DNA by the viral enzyme reverse transcriptase (RT). Although this enzyme is targeted by current anti-HIV-1 drugs such as AZT and nevirapine, virus drug-resistance is a continuing problem that will require alternative therapeutic options. The HIV laboratory has discovered new complexities in reverse transcription that have revealed possible new drug targets.

It was found that a viral protein called Tat enhanced reverse transcription and that its function is essential for HIV-1 replication. It has also been determined that Tat acts directly with RT to increase its activity. Experiments are in progress to discover exactly how Tat achieves this effect. Once this is determined it should be possible to identify compounds that can block Tat: RT interaction and prevent HIV-1 replication and AIDS. Although HIV-1 contains all the necessary machinery to initiate reverse transcription directly inside the virus, the process does not

begin until HIV-1 infects a cell.

However, HIV-1 can be induced to reverse transcribe in a test tube. This process is called natural endogenous reverse transcription (NERT) and detailed analysis shows that NERT differs from reverse transcription following infection of human cells.

This suggests that cellular factors play a critical role. Recent research showed that the cellular enzyme PKC influences an early step during infection that affects either entry into the cell and possible reverse transcription.

Virus-like particles (VLP) made by acute lymphocytic leukaemia cells and cultured cell lines have also been investigated. These VLP are found in a cellular compartment called a multivesicluar body (MVB).

Other RNA viruses such as Ebola and HIV-1 are known to traffic through MVB suggesting this VLP contains RNA. Identification of these VLP using UCSF Virochip technology is being undertaken in collaboration with Professor Joe DeRisi from the University of California, San Francisco. During the year, the HIV laboratory also co-organised the inaugural Australian Centre for Hepatitis Virology and HIV Virology Interest Group.

Queensland Institute of Medical Research

Immunology and Infection Dr Christian Engwerda Fiona Amante, Amanda Stanley, Kerri Clark Yonghong Zhou, Louise Randall

The Immunology and Infection Laboratory studies the host immune response during malaria and leishmaniasis, two important human parasitic diseases. In particular, researchers distinguish responses to parasites that lead to control of disease and those that contribute to tissue pathology The parasites causing malaria and visceral leishmaniasis can stimulate the host immunity to control infection and/or cause tissue pathology. Work on experimental models of cerebral malaria caused

by Plasmodium berghei and visceral leishmaniasis caused by Leishmania donovani has identified several key molecules and cells that cause tissue pathology associated with infection. Interestingly, these molecules and cells also play important roles in protection against infection, indicating they are either produced in excessive amounts or in inappropriate tissue locations.

Studies on experimental cerebral malaria using microarray analysis have identified several distinct immunological pathways that contribute to the pathogenesis associated with cerebral malaria.

Members of these pathways are potential targets for blockade to prevent cerebral malaria. Work on experimental cerebral malaria has confirmed that distinct mechanisms of cerebral malaria pathogenesis exist and tests are currently underway to see if cerebral malaria can be prevented by blocking candidate molecules identified in the microarray analysis.

Queensland Institute of Medical Research

Research on visceral leishmaniasis has revealed important, but distinct, roles for lymphotoxin a and tumour necrosis factor in the host immune response during experimental visceral leishmaniasis. It has been discovered that lymphotoxin α plays an important role in stimulating the expression of an important cellular adhesion molecule called VCAM1 in the liver following infection with Leishmania donovani. VCAM-1 expression in the liver is a critical event in the recruitment of immune cells to control parasite growth in this organ.

Important molecules that contribute to pathology during infectious diseases have been identified and strategies are being devised to limit the negative consequences of these molecules while retaining the activities that are important for controlling parasitic infection.

Leishmania donovani amastigotes in the liver (small cells with 2 purple spots) around a host macrophage (large purple nuclei). Parasites grow inside host macrophages before bursting out and re-infecting other cells

Highlights Discovered distinct roles for lymphotoxin α and tumor necrosis factor in the host response during visceral leishmaniasis Identified distinct immunological pathways contributing to the pathogenesis associated with cerebral malaria

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Infectious Diseases and Immunology Division

Immunoregulation Professor Anne Kelso Norbert Kienzle, Adriana Baz, Michelle Janas Penny Groves, Kathy Buttigieg, Stuart Olver Simon Apte, Kelly Kenney

The goal of the Immunoregulation Laboratory is to understand how CD8+ T lymphocytes acquire the ability to kill infected cells and tumours so that these processes can be controlled through improved vaccine design or immunotherapy

A: Detection of tumour antigen by flow cytometry shows that IL-4-secreting tumours (filled) are present at higher frequency than control tumour cells (open) among peritoneal exudate cells 12 days after tumour inoculation.

B: Mice inoculated with IL-4-secreting tumour cells are more prone to develop secondary tumours than mice given control tumour cells.

Highlights Found that IL-2 regulates perforin and granzyme gene expression in primary CD8+ T cells independently of its effects on survival and proliferation Showed that IL-4 secretion by tumour cells alters the tumor-specific CD8+ T cell response and leads to increased frequencies of secondary tumors in experimental models

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When CD8+ cytolytic T lymphocytes (CTL) interact with pathogen-infected or tumour cells, they release perforin and several enzymes known as granzymes. Perforin enables delivery of the granzymes into the target cell cytoplasm where they cause cell death. CTL also secrete cytokines, such as interferon-γ, that act on target cells and cells of the immune system to enhance pathogen or tumour elimination. The Immunoregulation laboratory is investigating ways to control activation and inhibition of CTL so that they express functions needed for host protection.

A core project seeks to understand how expression of the genes encoding perforin and three granzymes (A, B and C) is controlled during development of CTL from their non-cytolytic precursors.

Certain cytokines are known to be powerful regulators of CTL activity. It was recently found that the T cell growth factor interleukin 2 (IL-2) enhances expression of perforin and granzymes A, B and C independently of its effects on survival or proliferation. By using bcl-2-transgenic CD8+ T cells that survive without IL-2, it was further shown that primary induction of granzymes A, B and C requires both IL-2 and T cell receptor cross-linking

whereas perforin and IFN-γ can be induced by T cell receptor crosslinking alone.

Studies of the effect of IL-4 on tumour immunity continue. Tumour cells engineered to secrete IL-4 were cleared more slowly and gave rise to secondary tumours more frequently than control tumour cells. The laboratory has now shown that CD8+ T cells are required for tumour clearance in this model and that IL-4 secretion by the tumour alters the functional profiles of responding CD8+ T cells, inducing IL-4 and enhancing granzyme A and B expression. Further work is needed to determine whether these effects account for impaired tumour clearance. The work suggests that IL4 favours immune escape by tumours but might also be used to limit hostdamaging CTL responses.

Queensland Institute of Medical Research

Immunovirology Associate Professor Andreas Suhrbier Joy Gardner, Wayne Schroder, Grant Darnell May La Linn, Thuy T Le, Tahmineh Pirayesh Diem Hong Le, Itaru Anraku, Paweena Rattanasena

The Immunovirology Laboratory is exploiting new knowledge about interactions between viruses and the immune system to develop novel antiviral and anti-cancer strategies The Kunjin replicon vector technology, developed by Associate Professor Alexander Khromykh from The University of Queensland, has formed the basis of a new company Replikun Biotech Pty Limited which is seeking to explore the application of this technology for vaccine, gene therapy and protein production applications. Several joint patents have been filed and the new company has received funding from Start-Up Australia. HIV/SIV vaccine trials in monkeys are envisaged for the end of 2005 in collaboration with Associate Professor Stephen Kent from the University of Melbourne.

CBio Ltd has developed a novel anti-inflammatory compound, Cpn10, and under a contract R&D agreement, the Immunovirology laboratory was involved in establishing how this biological agent mediates its activity. Cpn10 appears to be able to limit the induction of inflammatory signals by agonists to some Toll-like receptors.

CBio Ltd has recently initiated a series of Phase II clinical trials in inflammatory conditions including rheumatoid arthritis, psoriasis and multiple sclerosis.

Queensland Institute of Medical Research

In collaboration with Dr T Antalis of the University of Maryland, USA, the laboratory discovered that SerpinB2 (PAI-2) is a retinoblastoma protein (Rb) binding protein. It has also been shown that SerpinB2 is able to protect Rb from the accelerated degradation mediated by human papillomavirus (HPV) E7, and that the rescued Rb silences HPV oncoprotein transcription in cervical cancer cells.

Continued efforts to understand the immunopathology of Ross River virus (RRV) disease have led to the discovery that this virus uses α1β1 integrin, a collagen IV receptor, as a receptor to infect mammalian cells.

The use of this receptor may explain how RRV can persist in synovial macrophages, since these cells upregulate α1β1 integrin expression upon entry into an inflammatory environment.

Kunjin replicon infected cancer cells

Highlights Vested the Kunjin replicon technology in a new biotech company Replikun Biotech Pty Limited, which has been formed with the help of capital from StartUp Australia Contributed to the characterisation of the anti-inflammatory activity of Cpn10, a new biological being developed by CBio Ltd for multiple sclerosis and other inflammatory conditions Illustrated that SerpinB2 silences transcription of the human papillomavirus oncoproteins in cervical cancer cells Demonstrated that α1β1 integrin, a collagen IV receptor is a receptor for the athritogenic Ross River virus

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Infectious Diseases and Immunology Division

Malaria and Scabies Professor David Kemp Katharine Trenholme, Katja Fischer, Tobias Spielman Anna Topping, Karen Anderson, Charlene Willis Wendy Chung

Malaria and scabies are infectious diseases which affect mainly Indigenous people, and for which there are no vaccines.

Identification of vaccine candidates and understanding of host immunity and evasion of this by the parasites are the major research activities undertaken in this laboratory

A female scabies mite in a burrow in the epidermis, with a trail of eggs (Medicalpicture)

Highlights Demonstrated that a SMIPP is a competitive inhibitor of a protease Found that CLAG 9 peptides are immunogenic in humans Determined that merozoites preferentially invade group A1 erythrocytes confirming the presence of a parasite lectin on the merozoite surface Developed a method for measuring commitment to gametocytogenesis in P. falciparum cultures Discovered a surprising spatial organisation of ETRAMPs at the malaria host-parasite interface

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Scabies is a major problem among Aboriginal people and new control measures against the causative agent, the mite Sarcoptes scabiei, are clearly needed. Work last year identified homologues of a number of house dust mite allergens in the laboratory’s cDNA sequence library.

A multigene family of homologues of the group 3 allergen gene, a serine protease was found. Surprisingly all except one of these had the triad of amino acids essential for catalysis mutated so they cannot be functional proteases and have been termed scabies mite inactivated protease paralogues (SMIPPs). The major advance this year is the expression of SMIPPs in Pichia pastoris, with the demonstration that a SMIPP can act as a competitive inhibitor of the protease chymotrypsin. This confirms the hypothesis that SMIPPs most likely mediate an immune evasion strategy that the parasite has evolved as an adaptation to parasitism, and this may present an unanticipated target for protective control measures.

Malaria is caused by infection with parasitic protozoa of the genus Plasmodium, and is transmitted by the bite of an infected Anopheles mosquito. The Malaria and Scabies laboratory works in collaboration

with the Malaria Biology laboratory in a number of areas.

Gametocytogenesis, the stage of the lifecycle essential for transmission of the parasite from the human to the mosquito host is being explored as a potential focus for intervention strategies.

Vaccine studies are being carried out with CLAG 9 which was previously identified in this laboratory. One member of a gene family of rhoptry protein(s), it may be involved in erythrocyte invasion by merozoites and has been implicated in cytoadherence, making it an attractive vaccine candidate molecule. Parasite invasion into the erythrocytes which differ in their ABO blood group are under investigation, and also a family of proteins called ETRAMPs located in the parasitophorous vacuole membrane. This membrane represents the interface between the intracellular malaria parasite and its host cell and plays a key role in parasite development. This research has revealed a surprising organisation of ETRAMP proteins in the parasitophorous vacuole membrane and, for the first time, shed light on the molecular architecture of this compartment.

Queensland Institute of Medical Research

Malaria Biology Dr Don Gardiner Dr Tina Skinner-Adams, Paula Hawthorne, Mathew Dixon Kathleen Klotz, Stephanie Kroeze

Malaria due to the parasite Plasmodium falciparum, remains the third leading cause of death due to an infectious disease worldwide. The Malaria Biology Laboratory is focused on understanding the biology of this complex organism to eventually develop new vaccines and therapeutic agents Prevention and treatment of malaria has become increasingly difficult due to drug resistance. Anti-malarial agents are now required to combat multi-drug resistant (MDR) malaria.

Drug combinations, including agents that have different targets, complimentary pharmacokinetic parameters and synergistic interactions are particularly important in the fight against MDR parasites as they can prevent the propagation of drug resistant parasite populations. Preliminary studies indicate that anti-retroviral protease inhibitors (ARPIs) may be useful in the treatment of malaria, particularly in individuals coinfected with HIV-1 – exciting results that suggest a novel group of drugs already available for clinical use may be useful against MDR malaria.

Completion of both the human and parasite genomes offers unprecedented opportunities for new insights, particularly in rationale drug design. In collaboration with Professor John Dalton of the University of Technology in Sydney, other potential targets for new antimalarial drugs are being investigated, specifically four amino peptidases believed to be involved in releasing amino acids from protein substrates Queensland Institute of Medical Research

in malaria cells. Because of their central role in protein turnover and synthesis in parasites they each represent a target at which novel anti-malaria drugs could be directed.

In conjunction with the Malaria and Scabies laboratory, this group is also investigating the role of chromosome 9 and the genes located in the deleted region in controlling cytoadherence, gametocytogenesis and agglutination, three phenotypes associated with virulence in P. falciparum.

Above: Connolly surface of the active site of plasmepsin II: Crystal structure of the complex between plasmepsin II and Rs370, a 30 nM inhibitor (left panel). Result of docking saquinavir to the active site of plasmepsinII using the program GOLD (right panel) Below: Cytoadherence of P.falcaiprum infected human red cells to a melanoma cell

Highlights Identified antiretroviral agents as potential anti-malarial drugs Identified which P. falciparum aminopeptidase is targeted by the anti-cancer drug Bestatin Identified a lectin like protein on the surface of merozoites

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Infectious Diseases and Immunology Division

Malaria Drug Resistance and Chemotherapy Dr Qin Cheng – Australian Army Malaria Institute Michelle Gatton, Darren Krause, Jennifer Peters Marina Chavchich, Karryn Gresty

This laboratory investigates mechanisms and processes involved in the development of drug resistance in malaria parasites and factors influencing the survival and spread of drug resistance

Highlights Identified two novel chloroquine resistant Pfcrt mutant alleles and established their origins and distribution in the Philippines Revealed that the amplification of pfmdr1 is associated with the development of resistance to artemisinin derivatives Established that triple mutation in DHFR with 0 or 1 mutations in DHPS have a high asymptomatic parasitological failure rate leading to increased transmission potential Determined the composition of var gene transcripts in ex vivo samples and determined the switch rates for several var genes Demonstrated the time required to achieve clinical immunity is proportional to parasite diversity and inversely proportional to transmission intensity Demonstrated an extensive genetic diversity in the PfHRP2 antigen which may cause up to 30% of falciparum parasites to not be effectively detected by PfHRP2based rapid diagnostic tests (RDTs)

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The development and spread of drug resistance in malaria parasites has lead to an increase in the morbidity and mortality of malaria in recent years. This laboratory has investigated both the origins and distribution of two novel chloroquine resistant Pfcrt mutant alleles in the Philippines and P. falciparum infection dynamics and transmission potential following treatment with sulfadoxine-pyrimethamine.

Artemisinin derivatives are currently the most promising therapy to treat drug resistant malaria. Although resistance to artemisinin drugs has not yet been observed in the field, experiences with all other antimalarial drugs indicate that there is a real risk of parasites developing resistance to these. Potential mechanisms of artemisinin resistance in laboratory selected parasites were investigated in collaboration with Dr D. Kyle at the Walter Reed Army Institute of Research, USA. The ability of P. falciparum parasites to vary the surface protein PfEMP1, is important for immune evasion and pathogenesis. Antigenic variation of PfEMP1 also plays an important role in the survival and spread of drug resistant malaria parasites. The rate of PfEMP1 variation has been estimated by measuring var gene transcripts

in ex vivo cultured parasites and parasite clones using conventional molecular analysis.

Recombinant fusion proteins of several dominant variants in E. coli have been expressed and used to examine the presence and specificity of antibodies in volunteers infected with 3D7. The extent of genetic diversity in P. falciparum Histidine Rich Protein 2 (PfHRP2) and its affect on the performance of PfHRP2based malaria Rapid Diagnostic Tests (RDTs) has also been investigated.

Above: Sulfadoxine resistance: Theoretical structural elucidation of sulfadoxine binding to the active site of P. falciparum DHPS

Queensland Institute of Medical Research

Molecular Genetics Associate Professor Peter Upcroft Jacqueline Upcroft, Linda Dunn, Rebecca Dunne Janelle Wright, Justin Ross, Sandra Prepens

This laboratory works on the two most common protozoan parasites of medical importance, the sexually transmitted Trichomonas vaginalis and the intestinal parasite Giardia duodenalis. Research areas include: determinants of drug resistance, virulence and pathogenesis, the sequencing, structure and plasticity of their genomes in relation to these traits, the development of new drugs and treatments, and their epidemiology Trichomonas vaginalis is an anaerobic, amitochondrial protozoan parasite of man. It is the most common sexually transmitted infection worldwide and infects about one billion people. T. vaginalis causes vaginitis, preterm delivery, low birth weight and increased infant mortality. It also predisposes to increased incidence of HIV/AIDS and is strongly associated with cervical cancer. The recommended treatment for this infection is metronidazole, but treatment failures and drug resistance are common.

Objectives in this laboratory are to understand mechanisms of drug resistance, pathogenicity and virulence, and ďŹ nd improved treatment strategies with novel drugs and targets. In the last year the focus has been on identifying mechanisms of clinical resistance in T. vaginalis and to this end, drug resistance lines against novel drugs have been generated.

Syngeneic lines (the parent susceptible strain and the drugresistant line derived from it) Queensland Institute of Medical Research

uniquely allow the identiďŹ cation of proteins expressed or overexpressed in the drug resistant line in comparison with the parent strain.

Membrane proteins over-expressed in a multidrug-resistant line are being targeted. Two unrelated drugs which are approved for human use are also currently being investigated.

Furazolidone was used successfully intravaginally to treat a patient with highly metronidazole-resistant parasites, and the second drug is an antiviral agent. A study was undertaken of antenatal patients in Port Moresby which used culture methods to determine a 70% prevalence for T. vaginalis. A study of antenatal patients in Colombo is currently being planned to verify low prevalence found by a colleague and the laboratory is also involved in a study of T. vaginalis among male AIDS patients in Los Angeles.

Completion of the sequencing of the T. vaginalis genome has greatly assisted studies identifying drug resistance genes, mapping studies, and studies on the great diversity and plasticity among different

isolates collected from around the world. This work parallels studies on genome plasticity and drug resistance in Giardia, particularly in regard to the subtelomeric regions.

Highlights Sequenced and annotated the Trichomonas vaginalis genome Genotyped and mapped the Trichomonas vaginalis genome Collected novel isolates from worldwide sources Developed novel drugs for treatment of the anaerobic protozoa Determined the extensive plasticity in both Giardia and Trichomonas genomes

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Infectious Diseases and Immunology Division

Molecular Immunology Professor Michael Good Colleen Olive, Michelle Wykes, Huji Xu Michael Batzloff, Manisha Pandey, Lynette Beattie Joanne Dyer, Jon Hartas, Jay Heise-Seabrook

The focus of this laboratory is the development of vaccines for diseases that affect some of the world’s most impoverished people Malaria kills over one million children each year, mostly in Africa.

The parasite evades immunity by rapidly changing its coat proteins and by destroying immunological memory. The coat proteins are recognised by antibodies which are able to kill parasites and inhibit their growth using a variety of mechanisms. However, by rapidly changing antigen expression and via allelic polymorphism, the parasite can enhance its survival.

Highlights Demonstrated that different lipopeptide constructs can induce self-adjuvanting immune responses to group A streptococcus Demonstrated that malaria infection causes apoptosis of parasite-specific memory B cells and plasma cells Demonstrated that attenuated infection with an ultra-low dose of parasites can induce immunity to multiple strains of malaria and that CMI appears to be a major component of protection

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The approach in this laboratory has been to enhance cell-mediated immunity (CMI) to target antigens which vary much less. Some of these antigens have been identified and approaches developed to boost CMI by administering attenuated or killed parasites in extremely low dose.

At the same time, the mechanism by which the parasite ablates immunological memory is being studied. Once these are understood, the objective is to design approaches to counter this and prolong immunity.

amino acid peptide that has been identified in the carboxylterminal region of the M protein, a surface protein and major virulence factor for the organism. Antibodies to the peptide can opsonise and destroy the organism. A method to fold this peptide (referred to as J8) into the α-helical form that the peptide adopts when present in its native configuration has been developed.

This was critical to inducing an immunogenic response. J8 has been linked to diphtheria toxoid and it has been shown that this conjugate vaccine is immunogenic and protective in an outbred mouse strain. The laboratory has received funding from NIH to conduct a clinical trial of a vaccine it has been developing for over 10 years. The phase I trial will occur at QIMR and a phase II trial is planned for Fiji, a country with a very high incidence of rheumatic fever and streptococcal pyoderma.

Group A streptococcus is an organism responsible for over 500,000 deaths per year, mostly due to rheumatic heart disease.

Streptococcal research in this laboratory is focusing on a 12 Queensland Institute of Medical Research

Molecular Parasitology Professor Don McManus Wenbao Zhang, Mary Duke, Mal Jones Jun Li, LiHau Zhang, Geoff Gobert Yuesheng Li, Magda Ellis, Julie Balen

This laboratory focuses on developing new interventions against parasitic worms of humans, particularly schistosome bloodflukes and the hydatid tapeworms, that will lead to their control Schistosomiasis and echinococcosis are two of the major diseases caused by parasitic worms.

Work on schistosomiasis in this laboratory includes large immunogenetic surveys in China where environmental and genetic factors involved in predisposition to infection are being dissected.

The molecular and cellular mechanisms leading to formation of fibrotic hepatic lesions, the major contributing source of the chronic disease are also being analysed. An intervention study was completed to show that buffalo infections are responsible for the persistence of human schistosomiasis transmission in China, work that has implications for future integrated schistosomiasis control directly influencing future health care policy there. This includes the use of chemotherapy for bovines and underpins the rationale for development and implementation of a veterinary-based vaccine for use in buffalo.

The characterisation of nuclear and mitochondrial genomes continues, along with investigation of molecular variation both in the genomes and in key molecules that may be the targets of new drugs and vaccines.

Molecular markers are being used to investigate genetic diversity. The Queensland Institute of Medical Research

Image 3. SjDLC immunolabelled for SjDLC1(red), tubulin (green), with DAPI counterstain (blue)

population structure of parasitic worm infections in Vietnam and the complete genome of Schistosoma japonicum is being sequenced, due to be finalised in late 2005. A microarray has been constructed that contains the majority of the schistosome transcriptome. This, along with proteomics analysis, is being used to investigate differential gene expression during different stages of the schistosome lifecycle, strain variation and the effect of drugs and vaccines on schistosome worms. The laboratory also focuses on schistosome iron metabolism, dyneins, secreted enzymes and surface molecules, including receptors, which are potential novel targets for drugs and vaccines.

A highly sensitive and specific blood test for diagnosis of patients infected with hydatid disease is being developed and researchers

are determining whether the method (based on a recombinant antigen, EpC1) can be applied for detection of the disease in sheep and marsupials.

Successful pilot vaccination trials against canine echinococcosis have been undertaken in China using recombinant antigens expressed by the mature adult worm and, with new NIH funding, these trials will soon be repeated.

Highlights Constructed and evaluated a microarray comprising the majority of the schistosome transcriptome Mapped the antibody epitope of the EpC1 protein and determined its function as a calcium binding molecule Completed successful pilot vaccine trials against canine echinococcosis

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Infectious Diseases and Immunology Division

Mosquito Control Dr Peter Ryan (Deputy Laboratory Head) Leon Hugo, Tim Hurst, Michelle Gatton Lynda Perkins, Kay Marshall, Jason Jeffery Tanya Russell, Tessa Knox, Anna Guerney

The Mosquito Control Laboratory, designated by the World Health Organisation as an official global Collaborating Centre for Environmental Management for Vector Control, specialises in designing new mosquito surveillance and control strategies

Laboratory Head, Professor Brian Kay, and Mrs Nguyen Thi Yen from the National Institute of Hygiene and Epidemiology, Hanoi, Vietnam, conducting field surveys for dengue mosquito immatures in southern Vietnam

Highlights Eradicated Aedes aegypti mosquitoes from 40 communes in northern and central Vietnam, resulting in the protection of 380,000 people from dengue and dengue haemorrhagic fever Used geographic information systems and spatial statistics to refine sampling strategies for medically important vector species, and define risk of Ross River virus and Barmah Forest virus diseases throughout Queensland Assessed native Australian freshwater fish species for use in Local Government mosquito control programs Developed innovative methods for determining insect age and risk of arbovirus transmission Evaluated microbial and sustained release biorational control agents against Ross River virus and Barmah Forest virus mosquito vectors

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This laboratory is part of the Australian Centre for International and Tropical Health and Nutrition linked to The University of Queensland and the School of Population Health. With the global resurgence in dengue and dengue haemorrhagic fever, collaborative research projects on surveillance and control of the global vector, Aedes aegypti have been extended.

Community based dengue control projects in collaboration with the Vietnam Ministry of Health and the National Institute of Hygiene and Epidemiology in Hanoi, have now successfully eradicated Aedes aegypti mosquitoes from 40 communes in northern and central Vietnam. To compliment this program, contemporary surveillance methods for dengue mosquitoes in a range of different water storage containers have been evaluated to help prioritise control efforts in other dengue endemic areas.

Research on age-grading methods for Australian mosquito vectors has continued in collaboration with Scott O’Neill at the University of Queensland and the Mosquito and Arbovirus Research Committee Inc. (MARC). Field evaluations of a cuticular hydrocarbon based method were conducted to determine the

age of Aedes aegypti mosquitoes and thereby define dengue transmission risk. A PCR-based gene expression assay to aid better understanding of the relationship between insect age and the transmission of a range of pathogens to humans, livestock or plants is also being developed.

The Mosquito Control Laboratory has worked closely with MARC, an independent organisation made up of representatives from Local Governments from Queensland, New South Wales and Victoria, and Queensland Health and industry.

Research projects have included: development of contemporary control strategies using microbial based insecticides, biology and ecology of Ochlerotatus procax and other freshwater arbovirus vectors in south-east Queensland, and Population genetics and vector competence of Ochlerotatus notoscriptus. Another project is developing practical control options for freshwater arbovirus vectors in Australia and will define the relative importance of different habitat types in terms and production of medically important vectors and evaluation of sustained release formulations of insecticides for control of freshwater species.

Queensland Institute of Medical Research

Tumour Immunology Dr Rajiv Khanna Maher Gandhi, Michael Rist, Judy Tellam Chrysoula Fazou, Geoffrey Connolly, Leanne Cooper Tania Crough, Eleanore Lambley, Natasha Webb

The major goal of the Tumour Immunology Laboratory is to obtain a deeper understanding of the mechanisms by which an immune response to tumors may be generated, augmented and applied to the inhibition of tumor growth The research interests of the Tumour Immunology laboratory are focused on understanding the role of virusspecific cellular immunity in the control of Epstein-Barr virus (EBV) and human cytomegalovirusassociated diseases. An important contribution of this work relates to research on EBV-associated tumours such as nasopharyngeal carcinoma and Hodgkin’s lymphoma.

this vaccine formulation is highly effective in inducing a protective immune response.

Preclinical work on the development of a therapeutic vaccine for these cancers has recently been published.

Based on these successful studies, the laboratory has been awarded a large grant from the National Institutes of Health (USA) to further refine this technology.

Further research in this laboratory focuses on human cytomegalovirus (HCMV) which causes birth defects in new born babies as well as serious clinical complications in transplant patients. Extensive studies have been carried out to delineate the mechanisms by which our immune system controls this virus. Based on these studies, a novel vaccine formulation has been developed which is aimed at preventing cytomegalovirus disease in both new born babies and transplant patients.

Preliminary testing has shown that Queensland Institute of Medical Research

Highlights Developed and commercially licensed therapeutic vaccine for nasopharyngeal carcinoma and Hodgkin’s lymphoma Preclinical testing of HCMV prophylactic vaccine showed promising results Developed HCMV immune monitoring diagnostic kit for transplant patients Demonstrated EBNA1 as a target for T-cell based immunotherapies for EBV-associated malignancies

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Cancer and Cell Biology Division Chair – Dr Kum Kum Khanna

The Cancer and Cell Biology Division consists of 12 laboratories located in both the Bancroft Centre and the Clive Berghofer Cancer Research Centre.

Research carried out in the Division covers a variety of topics to integrate investigations of the cellular, molecular and genetic basis of a wide range of cancers, including melanoma, leukaemia, breast, ovarian and colorectal cancer. Research themes include the normal mechanisms that control cell growth and stable inheritance of genetic information, identification of cancer susceptibility genes, development of mouse models to study in vitro functions of cancer genes, developing screening tools for early detection and devising normal strategies for the treatment and prevention of cancer.

The Division also collaborates in an important program with QIMR’s Population Studies and Human Genetics Division aimed at understanding environmental and lifestyle factors that contribute to cancer susceptibility.

In addition, there are research interactions with the University of Queensland and various hospitals that have helped translation of research findings into patient care.

The acquisition of a Live Cell Imaging system this year gives researchers faster access to high quality fluorescence microscopy and the ability to image protein localisation, functions, molecular interactions, and signalling networks in real-time in living cells. The investment in high-throughput technologies such as Illumina BeadStation will enable our scientists to generate genome-wide expression profiles for multiple samples on a single BeadChip. The Illumina BeadStation is also designed to generate reproducible profiles from degraded RNAs such as those derived from formalin-fixed, paraffin-embedded tissues – a feat not possible with cDNA microarray. The machine also supports analysis of differences in single nucleotide polymorphism (SNP) allele frequencies between cancer cases and controls in large numbers of samples. This technology ensures the Division maintains an internationally competitive edge.

Cancer Genetics Cancer Immunotherapy Dendritic Cells and Cancer Human Genetics Leukaemia Foundation Membrane Transport Molecular Cancer Epidemiology Molecular Pathology QCF Transgenics Radiation Biology and Oncology RBWH Conjoint Gastroenterology Signal Transduction

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Queensland Institute of Medical Research

Cancer Genetics Dr Georgia Chenevix-Trench Jeremy Arnold, Nicola Waddell, Jonathan Beesley Anna Marsh, Xiaoqing Chen, Helene Holland Aaron Lewis, Nicci Wayte

The Cancer Genetics Laboratory aims to understand why some people get cancer and how cancer develops from a normal cell.

Of particular interest are breast and ovarian cancer which are often found together in the same families and share many similar characteristics The majority of research in the Cancer Genetics laboratory is focused around two major Australian resources, the Kathleen Cuningham Foundation for Research into Familial Breast Cancer (kConFab) and the Australian Ovarian Cancer Study.

In collaboration with Dr Khanna of the Tumour Immunology laboratory, researchers have evaluated the function of the CHEK2 1100delC truncating SNP and found it associated with a two-fold increased risk of breast cancer. Analyses of expression and phosphorylation suggest that the truncating variant is likely to act by haploinsufficiency, but that some compensation occurs to allow normal degradation of Cdc25A which might explain the low risk associated with the variant.

Collaborations with overseas researchers have helped identify a group of more than 1800 BRCA1 and BRCA2 carriers to look for modifier genes that might help to explain the variable expression and penetrance of mutations in these genes. Analysis carried out by Dr Spurdle of the Molecular Cancer Epidemiology laboratory suggests that, in contrast to previous reports, the repeat polymorphism in the AIB1 gene does Queensland Institute of Medical Research

not modify the breast cancer risk in BRCA1 or BRCA2 carriers.

Work with Dr Berchuck from Duke University in North Carolina, USA, has shown that a variant in the promoter of the progesterone receptor gene appears to reduce the risk of endometrioid and clear cell ovarian cancer. This finding has been replicated by two other groups and is possibly the first bone fide ovarian cancer susceptibility gene to be described.

In conjunction with researchers at the Sanger Centre in the UK, the laboratory reported the existence in mutations in the ERBB2 gene in lung cancers and a borderline ovarian cancer. That about 10% borderline serous ovarian tumours carry mutations in this gene has since been confirmed, and the functional consequences of this mutation, and others in BRAF and KRAS are now being evaluated.

Highlights Found that a promoter variant of the progesterone receptor gene protects against the risk of endometrioid and clear cell ovarian cancer Evaluated the mechanism of action of the CHEK2 1100delC variant which is associated with a two-fold increased risk of breast cancer Identified mutations in ERBB2 in borderline serous ovarian tumours

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Cancer and Cell Biology Division

Cancer Immunotherapy Dr Chris Schmidt Professor Kay Ellem, Nathan Martinez, Cathy Lanagan Linda O’Connor, Michael Hamilton, Xiang Huang Michelle Neller

The immune system has the power and specificity to eradicate cancers, with few side-effects. This laboratory develops treatments for solid tumours, based on boosting the anti-tumour immune response in patients

Manufacturing the autologous dendritic cell-based vaccine used in melanoma tumour treatment

Highlights Current Phase III trial for patients with early metastatic melanoma (Stage IIIB/C) reached 1/3 of planned accrual Dendritic cell-based vaccines proved capable of inducing durable, complete clinical responses in a patient with metastatic prostate cancer Analysis of bloods from patients with advanced melanoma following dendritic cell vaccination showed that precisely those patients with ex vivo anti-tumour T cell responses experienced durable, complete clinical responses Attained proof-of-principle that a combined anti-angiogenic and antitumour T cell immune response can eradicate poorly immunogenic cancers in a murine model

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Melanoma has been a particular focus of tumour immunotherapy research, having a long history of response to treatments based on the vaccine approach. In conjunction with Prof Michael O’Rourke from Mater Hospital, an autologous dendritic cell-based vaccine has been used to treat patients with advanced metastatic melanoma.

Several patients had complete remission of their melanomas, durable to date with an average of over 4 years. The success of these trials led to a new trial for prostate cancer with Dr Frank Gardiner from the University of Queensland, and the Northern section of the Urological Society of Australia.

Critical goals for the next year are establishment of more efficient methods to generate dendritic cells from the blood of patients, testing of these cells in a clinical trial, and continuing research into the characteristics of a successful antitumour T cell response.

any of several relevant cytokines, the encapsulated cells can be injected into tumours, initiating combined anti-angiogenic and cell-mediated immune responses.

In murine cancer models, this approach is capable of complete eradication of cancers that resist other forms of immunotherapy.

Encapsulation confines the cytokines to the tumour, thus avoiding the toxic effects of many cytokines when they enter the systemic circulation.

Due to its generic nature, the depot cytokine strategy will advance the speed with which this potential therapeutic intervention in cancer can be given. Now that the proofof-principle has been established in mouse models, the first clinical trial of this approach is being planned, initially with canine patients.

The Depot Cytokine Group (KE, MH, XH) have successfully developed novel technologies for the encapsulation in an inert, biocompatible matrix, of a highly selected subline of HEK293 cells capable of resisting the intratumoural environment. Once transfected with Queensland Institute of Medical Research

Dendritic Cells and Cancer Associate Professor J Alejandro López Tammy Maxwell, Alberto Pinzón-Charry, Jacqui Fleming Sandro Prato, Marta Sloniecka, Mitchell Arico

Dendritic cells (DC) are potent initiators of the immune response currently used in novel therapies for melanoma, prostate and glioblastoma at the QIMR. This laboratory explores the function of DC in patients with cancer and healthy donors, and studies the mechanisms responsible for the success achieved with DCbased immunotherapy clinical trials A completed evaluation of 120 women with various stages of breast cancer established the presence of high numbers of immature/ dysfunctional cells occupying the DC compartment. Although sharing some properties of bona fide DC, their capacity to efficiently present antigen is significantly reduced.

Of interest, this population was also observed in patients with advanced prostate cancer (10) and glioblastoma (6). While present in very small numbers, the functional characterisation of these cells in healthy individuals has been completed to show that they behave as the same cells from patients with cancer, and a direct correlation between the severity of the clinical status and cell numbers was also found. Although this immature population is poorly responsive to most maturation stimuli, CD40 ligand renders them mature and activated. This finding opens the possibility for clinical intervention when DC are required from patients with advanced cancer. The increased number of these immature cells (DR+IC) is now proposed to play an important role in disease development.

Queensland Institute of Medical Research

The laboratory studies the requirements for antigen loading using RNA as an antigen source and this year, in collaboration with Professors Vasso Apostolopoulos and Geoffrey Pietersz from the Austin Research Institute in Melbourne, investigated novel strategies improving RNA loading into DC. This project was funded by the QCF and developed together with Associate Professor Michael McGuckin.

In collaboration with Dr Giampietro Corradin from the Université de Lausanne Switzerland, the analysis of pathways of antigen presentation by DC using a synthetic protein model has now been completed and results using specific drug inhibitors show that various pathways of intracellular presentation are involved in the process. Another project which investigated the benefits for DC culture derived from using a novel synthetic support, providing an environment resembling the extracellular matrix, was undertaken in collaboration with Tissue Therapies, Brisbane.

Above: Tumour-induced DC dysfunction generates ineffective immune responses

Highlights Identified immature cells (DR+IC) in advanced cases of glioma, breast and prostate cancers Completed detailed characterisation of DR+IC in healthy individuals Found that DR+IC are responsive to CD40 ligand Discovered that antigen presentation of a synthetic protein

by DC requires endosomecytosol transport and vacuolar acidification and protease activity in the lysosome

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Cancer and Cell Biology Division

Human Genetics Dr Nicholas Hayward Graeme Walker, Sandra Pavey, Derek Nancarrow Jane Palmer, Mitchell Stark, Herlina Handoko Heather Smith, Cheryl Filipich

The major focus of this group is to identify novel cancer genes and study the way in which defects in these genes are associated with cancer predisposition or development. Key approaches include genome-wide linkage analysis, candidate gene mutation screening, gene expression profiling, cellular profiling and transgenics

Above: Melanocytes cultured from Hras transgenic mice.

Gene expression profiling was used to identify a molecular signature characteristic of PTEN mutation status in a panel of 60 melanoma cell lines. Using siRNA and drug inhibitors, a number of the differentially expressed genes are currently being investigated to determine whether they are downstream effectors of the PI3K pathway and could be useful targets for therapeutic intervention to treat melanoma.

Below: Pancreatic islet tumours staining for insulin in mice lacking the Men1 gene

Highlights

Using strains of transgenic mice, it has been demonstrated that combined activation of the Hras and Cdk4 oncogenes predisposes mice to melanoma. These tumours can arise spontaneously and are often highly metastatic, thus providing a useful model of the human disease.

In other studies of melanoma and oesophageal cancer, a number of promising chromosomal regions showing copy number variation have been found. These are potential sites at which novel tumour suppressor genes and oncogenes reside. Studies to identify some of these genes are ongoing.

Showed that mice carrying simultaneous activating mutations in the Hras and Cdk4 oncogenes spontaneously develop metastatic melanoma Showed that cutaneous melanoma predisposition was not associated with variants of the EGF gene Identified a gene expression profile associated with mutation of the PTEN gene Identified novel regions of chromosomal gain or loss in cutaneous melanoma using array-based comparative genomic hybridisation (aCGH) Identified novel regions of chromosomal gain or loss in oesophageal cancer using (aCGH) Reported that activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS

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Queensland Institute of Medical Research

Leukaemia Foundation Professor Andrew Boyd – The University of Queensland Nirmitha Herath, Jason Lickliter, Mark Spanevello Brett Stringer, Fiona Smith, Jacinta Carter Jenny Reeder, Joanne Cox, Ke Chen

The Leukaemia Foundation of Queensland Laboratory is seeking to understand the role of critical cellular proteins in the causation and evolution of leukaemia and other cancers.

Funding for this laboratory is provided largely by the Leukaemia Foundation Eph and ephrin membrane proteins in cancer When Eph and ephrin proteins on adjacent cells bind together they initiate bidirectional signals which affect the cytoskeleton and adhesion proteins generally resulting in deadhesion and contact repulsion.

Paradoxically, in certain situations these interactions can lead to increased adhesion to other cells or to extracellular matrix proteins.

These interactions have critical roles during embryonic development and in pathological states, notably in cancer. Recent work on the structural basis of Eph-ephrin interaction has shed light on the determinants of the outcome of Eph-ephrin signalling. These studies have also paved the way for the development of antibodies and antagonists for EphA3, a protein expressed on a high proportion of metastatic melanomas and other human tumours, as potential cancer therapeutics.

Fat protocadherin Fat is an adhesion molecule which is involved in normal development and in kidney function. An abnormal form of this protein is expressed in some forms of T cell leukaemia and lymphoma. This abnormal Queensland Institute of Medical Research

form inhibits the normal fat protein and may thus contribute to tumour spread.

CD44 A group headed by Professor David Gotley, from The University of Queensland, is studying the role of the CD44 protein in tumours.

A spliced form of CD44 normally seen only during development is reexpressed in cancers. This form of CD44 confers metastatic properties on tumours.

Apoptosis inhibitors Another group, headed by Dr Jason Lickliter, studies the overexpression in tumours of proteins which inhibit programmed cell death. One example is the causative role of increased expression of bcl2 in follicular lymphoma. A novel anti-bcl-2 drug has been shown to induce cell death in tumours.

Another project explores ways of circumventing resistance to Glivec, a therapeutic molecule targeted against the Bcr-Abl oncoprotein in chronic myeloid leukaemia.

A. Fat expression in 26 hours post fertilisation (hpf) zebrafish embryo (vz – ventricles, ov-optic vesicle, L-lens) B. 33 hpf embryo showing expression in the intestinal bulb (ib) C. 50 hpf embryo showing expression in branchial arches (ba)

Highlights Analysed structure-function of Eph and ephrin proteins using a novel mutagenesis strategy Progressed development of potential therapeutics which target Eph proteins Expressed the fat protocadheri in early vertebrate development

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Cancer and Cell Biology Division

Membrane Transport Dr Nathan Subramaniam

Daniel Wallace, Lesa Summerville, Patricia Lusby

The liver plays a major role in the regulation of iron metabolism.

The main focus of this laboratory is understanding how liverexpressed proteins sense iron levels and how they regulate the absorption and distribution of iron within the body

Liver biopsy showing iron deposition in juvenile haemochromatosis

Highlights First identification of iron overload or ferroportin disease due to mutations in the ferroportin gene in the Indian subcontinent Demonstrated that the Val162 deletion of the ferroportin gene is also found in Asia – confirming that it is the most common and prevalent mutation in ferroportin Identified juvenile haemochromatosis in Australia due to mutations in the hemojuvelin gene for the first time

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The appropriate level of iron in the body is maintained through the regulation of its absorption in the duodenum. It is now clear that the liver plays a very important role in regulating the level of iron in the body. This laboratory has been studying the role of several liver expressed proteins, HFE, transferrin receptor 2, ferroportin, hemojuvelin and hepcidin in this very important pathway.

Mutations in all of these genes are associated with various forms of the iron overload disorder hereditary haemochromatosis. This laboratory was first to identify the basis of juvenile haemochromatosis in Australian patients and has recently shown that mutations in hemojuvelin in these patients result in this disease, a form of iron overload which presents early in life and can cause severe organ dysfunction if not detected and treated. It also found that coinheritance of HFE and hemojuvelin mutations does not cause increased iron loading.

patient from the Indian subcontinent.

Laboratory studies also suggest that the Val162 deletion of the ferroportin gene is the most prevalent mutation in non-HFE haemochromatosis.

An initial characterisation of a new mouse model of type 3 haemochromatosis, the transferrin receptor 2 knockout mouse, has been performed to show that it develops significant iron overload even when fed a normal diet. Future research is aimed at its complete characterisation and identifying the role of this protein in regulating iron metabolism. These and other studies in the laboratory will give further insight into the biology of these iron-related disorders with a view to developing therapeutics for their treatment.

In a collaborative study with Professor Peter Browett at the University of Auckland, the laboratory demonstrated, for the first time, the presence of iron overload due to ferroportin disease in a Queensland Institute of Medical Research

Molecular Cancer Epidemiology Dr Amanda Spurdle Paul Lovelock, Joanne Young, Felicity Lose Sue Healey, Melissa Barker, Leigh Fraser Lesley Butterworth, Michael Walsh, Genevieve Birney

Both environment and genetics contribute to the genesis of common cancers such as those of the endometrium, breast, ovary and colon. This laboratory seeks a comprehensive understanding of how these factors interact in the population in order to develop avenues for prevention Work assessing the cancer-causing potential of subtle variants of the known breast cancer predisposition genes BRCA1 and BRCA2 has continued. Application of a mathematical model has formally classifed 13/29 variants as being of low clinical significance, based on genetic and tumour histopathology.

Functional studies on two variants have supported their classification from non-functional approaches.

Radiosensitivity analysis on lymphoblastoid cell lines from individuals with known BRCA1 mutations, and normal controls, have been completed to show that great variation in assay responses across the groups will confound classification of variants based on these assays.

From studies assessing proteins that interact with BRCA1 as potential breast cancer genes, it has been shown that there are no gene mutations and no significantly altered expression of the gene transcript for the novel genome maintenance protein BIX in normal cells from familial breast cancer patients, and that the double-strand break repair gene Rad51 gene is not mutated in familial breast cancer patients.

Queensland Institute of Medical Research

In collaborative work with Drs Chenevix-Trench and Webb, no significant breast cancer or ovarian cancer risk associated with several double-strand break repair gene common variants previously suggested to be associated with increased cancer risk have been found.

Research led by Dr Joanne Young has shown that, in addition to the traditional model of cancer development from adenomatous polyps, colorectal cancers may develop from serrated polyps.

Studies of this ‘serrated pathway’ have been extended to describe a novel familial syndrome of colorectal cancer predisposition which evolves through serrated precursor lesions, termed the serrated pathway syndrome or SPS. Further studies have lead to the mapping of two genomic regions of linkage, and candidate genes within these regions are currently being identified.

The potential key outcome of this project will be the definition of the underlying genetic predisposition to develop serrated neoplasia.

Recognition of this syndrome, with possible presymptomatic testing, will allow families to be monitored for the lesions that act as aggressive

precursors to their colorectal cancers, thereby preventing cancer and potential deaths.

Highlights Formally classified a significant proportion of BRCA1 and BRCA2 variants previously of unknown clinical significance Developed and applied assays to assess the function of variants of BRCA1 and BRCA2 Described a novel syndrome of familial colorectal cancer (SPS) Established areas of linkage to two genomic regions in SPS kindreds

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Cancer and Cell Biology Division

Molecular Pathology Professor Sunil Lakhani – The University of Queensland Catherine Clarke, Peter Simpson, Suzanne Parry Allison Jones, Anastasia Sofronis

The Molecular Pathology Laboratory studies the genetics and cell biology of breast cancer to improve the classification and diagnosis of the disease The Molecular Pathology laboratory arrived at QIMR as a group in Oct 2004, directly from London.

Since then, the laboratory has been established, and in particular, ethical clearance has been obtained from the Royal Brisbane and Women’s Hospital to collect surgical specimens of breast tissue from consented patients.

This bank of frozen normal and tumour tissue will be used by the laboratory, and through a collaboration with the Australian Biospecimens Network (ABN), is available to other researchers with ethical approval across Australia.

Tissue microarrays (TMA) of familial breast cancers have been created for the KConFab organisation with whom the laboratory collaborates and creation of a series of TMAs of >1000 cases of sporadic breast tumours has also begun. These TMAs will be invaluable in future studies for screening novel markers of breast tumour subclassification and correlating with patient survival.

Top left: Triple immunofluorescent labelling of normal breast epithelium for Ck5/6, Ck8/18 and SMA

Highlights Establishment of the new laboratory at QIMR Tissue microarrays of familial breast cancers created

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Top right: Immunohistochemistry for known (S100A2, TP63) and novel (14-3-3s, SPARC) myoepithelial cell markers which aid diagnostic practice and characterisation of breast carcinomas with myoepithelial/basal phenotype Below: Comparative genomic hybridisation of a breast pleomorphic lobular carcinoma in situ

Queensland Institute of Medical Research

QCF Transgenics Dr Graham Kay Arne Mould, Ian Tonks, Sonia Greco Patricia Keith, Michelle Martinez, Rakesh Prasad

The Queensland Cancer Fund (QCF) Transgenic Laboratory studies cell and developmental biology with particular emphasis on using transgenic and knockout mice. Major areas of research are epigenetic control of gene expression during development, angiogenesis or new blood vessel growth as a target for treatment in cancer, and cellular control of growth and differentiation X chromosome inactivation (XCI) is a developmental process operating in female mammals to compensate for X-linked gene dosage differences between males and females. XCI is a model system for studying the epigenetic control of gene expression both in normal (eg during embryonic development and adult tissue maintenance) and disease states such as cancer. This laboratory studies the role that the Xist and Tsix genes play in XCI by controlling chromosome counting and choice, the initiation and spread of gene inactivation, and its stable maintenance. These master genes orchestrate the epigenetic mechanisms that ultimately control gene expression by changing chromatin ultrastructure.

Other research studies the involvement of Vegf-B, a member of the vascular endothelial growth factor family, in developmental and pathological angiogenesis (new blood vessel growth). While angiogenesis is essential during development and in normal processes such as wound healing, it is detrimental in cancer and arthritis where it facilitates disease progression. Understanding the Queensland Institute of Medical Research

precise function of angiogenic factors is essential for designing antiangiogenic treatment strategies.

The laboratory also investigates the pocket protein family as a major axis of control for cell cycle progression and cellular differentiation during development and in cancer. This project concentrates particularly on the role of pocket proteins in melanocyte homeostasis and in preventing their progression to melanoma.

(A) Mice with melanocyte speciďŹ c knockout of Rb show no loss of pigmentation in vivo compared to normal mouse (B) Melanocyte in ear skin stained with DOPA

Highlights Found that the Xist knockout forces primary non-random X inactivation which indicates that the 5’-repeat is uniquely involved in chromosome choice during X inactivation Demonstrated that transgenic overexpression of VEGF-B isoforms by endothelial cells potentiates postnatal vessel growth both in vivo and in vitro Showed that melanocytes in conditional Rb-/- mice are normal in vivo but exhibit proliferation and pigmentation defects in vitro

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Cancer and Cell Biology Division

Radiation Biology and Oncology Professor Martin Lavin – The University of Queensland Nuri Gueven, Cheng Peng, Natalie Rundle Philip Chen, Sergei Kozlov, James Brown Amila Suraweera, Richard Laherty, Liam St Pierre

The major focus in this laboratory is the recognition of damage in DNA employing human and animal models to investigate genome instability, cancer predisposition and neurodegeneration. Research is also directed toward isolating novel therapeutic compounds from snake venom and early detection of prostate cancer

Highlights Demonstrated that DNA-PK controls the activity of ATM defective in ataxia-telangiectasia Identified Mre11 as a substrate for ATM/ATR Cloned and characterised Factor-X like protease genes in Australian elapid snakes Showed that Mre11 missense mutant N117S has a dominant interfering effect on wild type protein

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The gene defective in the human genetic disorder ataxia-telangiectasia (A-T), ATM, plays a central role in recognising double strand breaks in DNA and signalling these breaks to slow the passage of cells through the cell cycle so the DNA damage can be repaired. Failure to recognise and repair this damage in A-T patients results in increased frequency of cancer and progressive neurodegeneration. Being able to slow or halt the progress of this neurodegeneration would be of great benefit to A-T patients. This laboratory previously showed that a novel isoindoline nitroxide was capable of preventing some of the neurological features in ATM mutant mice and studies are in currently in progress to determine whether this compound protects against neurodegeneration.

Investigations are continuing on a novel downstream substrate for ATM called Mre11 which also plays a key role in maintaining the integrity of the genome. The functional consequences of the phosphorylation reaction involved are being delineated. It has been demonstrated that autophosphorylation and activation of ATM involves several

separate phosphorylation sites on the molecule. Since A-T is one of several related syndromes characterised by ataxia, investigations are underway on whether other related human ataxia’s might also feature a reduced capacity to deal with different forms of damage in DNA. It has also been shown that the protein Aprataxin, defective in ataxia with oculomotor apraxia type 1 (AOA1), is involved in the recognition and repair of single strand breaks in DNA. Work is currently underway on the gene product Senataxin, defective in a related syndrome AOA2, and on other novel forms of AOA with a view to determining whether the proteins involved participate in the DNA damage response.

Other projects in the laboratory include the isolation of genes and proteins from Australian snakes with a view to developing human therapeutics, the establishment of mulitiple markers for early detection and prognosis of prostate cancer and delineation of pathways of development in lower eukaryotes.

Queensland Institute of Medical Research

RBWH Gastroenterology Associate Professor Barbara Leggett Vicki Whitehall, Sarah-Jane Cozzi, Kevin Spring Ron Buttenshaw, June Chia, Elise Pelzer Rachael Price, Catherine Bond, Kim Loh

The Royal Brisbane and Women’s Hospital (RBWH) Gastroenterology Laboratory is characterising the genetic changes underlying the progression of a pre-cancerous colonic polyp to colon cancer to increase understanding of this disease and improve treatment options. Both polyps and cancers are studied in an effort to identify genetic markers for progression, prognosis and response to therapy Unlike most other internal cancers, bowel cancer can be prevented by examination of the bowel by a procedure called colonoscopy.

During colonoscopy the small polypoid growths in which bowel cancer develops can be removed.

The Gastroenterology laboratory focuses on better understanding the different types of polypoid growths that occur in the bowel, who is most likely to have these and which polyp types are most likely to turn into cancers. Genetic changes in different types of polyps and a wide range of bowel cancers are studied.

Access to a large number of polyps and cancers collected from patients treated at the Royal Brisbane and Women’s Hospital over many years is crucial in this work. The laboratory is extremely grateful to these patients who have kindly consented to have excess tissue from removed polyps and cancers used for research.

The subset of cancers that have frequent gene methylation and often a high level of microsatellite instability have been of particular interest this year. These tumours frequently have oncogenic mutations in a growth regulatory gene called Queensland Institute of Medical Research

BRAF and seem to evolve from large, proximal hyperplastic polyps.

This finding is changing clinical practice by making colonoscopists more aware of the importance of removing this type of polyp and of following up such patients in case they develop further polyps. Cancers which arise from these polyps have quite different genetic alterations when compared to other bowel cancers, as well as different clinical features. Despite responding less well to conventional chemotherapy, these cancers usually result in a more favourable prognosis. Because of the importance of more fully understanding the genetic basis of these differences, methylation changes in important cell growth regulatory genes such as BMP3, THBS4 and KLF4 are being examined. A better understanding of these genetic changes may lead to improved therapy for patients.

A colonic polyp observed at colonoscopy.

Highlights Demonstrated which subset of polyps most frequently bear BRAF mutations and therefore are the likely precursors of heavily methylated cancers Identified specific genes heavily methylated and down regulated in some bowel cancers

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Cancer and Cell Biology Division

Signal Transduction Dr Kum Kum Khanna Aaron Urquhart, Derek Richard, Megan Fabbro David Young, Emma Bolderson, Karen Hobson

The goal in this laboratory is to understand signal transduction pathways involved in the detection, signalling, or repair of DNA damage, an area of critical importance to cancer research

Highlights Found that 1100delC mutation in CHEK2 acts as haploinsufficient for tumour suppression Completed functional characterisation of a novel protein involved in regulation of cytokinesis Discovered that protein phosphatase, PP2A, plays an important role in regulating activity of ATM kinase Found that histone acetyltransferase MOF, influences the functions of ATM

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Several genes are involved in the DNA damage response pathways.

ATM, BRCA1, BRCA2, CHK2 and p53 contribute to breast cancers.

Research in this laboratory attempts to identify other known or novel genes in these pathways which might have similar involvement in cancer susceptibility by preventing the generation of mutations in human DNA. Evidence has been provided that the protein truncating variant of CHEK2, 1100delC, is associated with a moderate increase in breast cancer risk, although the variant is rare in Australia. Analyses of expression and phosphorylation of wild type CHK2 in lymphoblastoid cell lines established from heterozygous carriers, suggested that the variant is likely to act by haploinsufficiency and analysis of CDC25A degradation, a downstream target of CHK2, suggests that some compensation occurs to allow normal degradation of CDC25A. Such compensation of the 1100delC defect in CHEK2 might explain the rather low breast cancer risk associated with the CHEK2 variant.

A novel protein implicated in breast cancer progression, Cep55, has been functionally characterised.

CEP55 silencing by siRNA induces several cytokinesis defects including multinucleation, cells arresting at the midbody stage, and multipolar

spindle formation, changes which are characteristic of cancer cells. A nuclear localisation signal (NLS), 385KRKK388, has been mapped within the amino terminus of ATM and it has been demonstrated that ATM is imported in the nucleus by conventional import receptor, importin α/β heterodimer. Analyses of various ATM deletion constructs uncovered a requirement for the amino terminus of ATM for its association with chromatin and for optimal kinase activity. Protein phosphatase 2A has been identified as an important regulator of ATM activation.

In collaboration with Dr Pandita, Washington University School of Medicine, USA, the regulation of ATM activity by histone acetyltransferase, MOF was studied to show that expression of a dominant negative mutant hMOF or by RNAi-mediated hMOF knockdown, results in decreased ATM autophosphorylation, ATM kinase activity, phosphorylation of downstream effectors of ATM and DNA repair while increasing cell killing. In addition, decreased hMOF activity is associated with loss of the cell cycle checkpoint response to DNA double strand breaks (DSBs).

These results suggest that hMOF influences the function of ATM.

Queensland Institute of Medical Research

Population Studies and Human Genetics Division Chair – Dr Greg Anderson

The Population Studies and Human Genetics Division utilises a wide range of contemporary epidemiological, genetic and molecular techniques to investigate a spectrum of diseases relevant to the Australian population. The Division has a particular strength in cancer research with broad programs in skin, ovarian, oesophageal, head and neck and liver cancer. Scientists in the Division also make extensive use of twins to analyse the relative importance of genes and environment in a variety of important health problems and traits including endometriosis, drug and alcohol dependence, asthma, pigmentation, fertility and cognitive ability. Another long term research initiative has been in the area of gastrointestinal disease, with studies on liver fibrosis, paediatric cholestasis, alcoholic liver disease and disorders associated with body iron overload such as hemochromatosis. Together, these conditions place an enormous burden on the Australian health care system and it is only by understanding their prevalence, aetiology and basic biology that we can move towards prevention and more effective therapies.

Many of the Division’s projects make extensive use of large population studies to investigate patterns of disease and the Division is indebted to the public for their continued goodwill in helping to make so much of this research possible. The collection of epidemiological and clinical data allows researchers to correlate patterns of disease with environmental factors, and blood and tissue samples enable a variety of genetic and basic molecular analyses to be carried out. The need to conduct large-scale studies means that and the Division possesses extensive resources for high throughput genotyping and gene expression analysis. These population and genetic approaches are complemented by detailed biochemical and cellular studies to investigate mechanisms of disease and identify potential therapeutic targets.

The Division’s scientists are its greatest resource and our staff continue to make key contributions to the scientific community locally, nationally and internationally. It is through the combined efforts of epidemiologists, clinicians, nurses, molecular biologists and chemists that significant heath problems can be addressed in a comprehensive, efficient and highly effective manner.

Cancer and Population Studies Genetic Epidemiology Hepatic Fibrosis Iron Metabolism Melanoma Genomics Molecular Epidemiology

Queensland Institute of Medical Research

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Population Studies and Human Genetics Division

Cancer and Population Studies Professor Adèle Green Penny Webb, David Whiteman, Melissa Merritt Maricel Hughes, Jillian Ramsden, Karen Martin Cathy Baxter, Shahram Sadeghi, Doug Lincoln

The Cancer and Population Studies Group investigates the causes of cancer and other chronic diseases to develop avenues for their prevention

Highlights Obtained first evidence that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce a person’s risk of skin cancer Found that smoking and obesity greatly increase the effects of acid reflux in the development of Barrett’s oesophagus On-going Nambour residents skin cancer study reached its 19th year of data collection Recruitment of cases for national study of ovarian and oesophageal cancer neared completion with over 3000 cases recruited to date Data collection continued from participants via questionnaires, interviews, tumour blocks, blood and tissue samples

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Over the past five years the Cancer and Population Studies Group has conducted nationwide studies of cancers of the ovary and oesophagus, using a combination of epidemiological methodology and genetic analyses of blood and tumour tissue to identify their causes. Clinical and research collaborations across Australia have enabled recruitment of several thousand people with these cancers and related conditions, along with cancer-free people with whom to compare environmental exposures and expression of various relevant genes.

A separate study examines the premalignant condition, Barretts oesophagus, which is strongly related to adenocarcinoma of the oesophagus. In another project related to ovarian cancer, the quality of life of women with ovarian cancer is being examined in relation to receiving palliative chemotherapy for very advanced disease.

Follow-up on the occurrence of skin cancers in some 1,000 residents of the Queensland township of Nambour who were participants in the Nambour Skin Cancer Prevention Trial (1992-1996) is now in its nineteenth year. Information

relevant to sun exposure, general lifestyle, other sun-related disease, and occurrence of other cancers and serious diseases as well has been collected. A major project funded by the World Cancer Research Fund is dedicated to clarifying the role of diet in skin cancer through these same residents. Researchers are also collaborating with a European consortium to study links between skin cancer and human papilloma virus skin infections.

Collaborative research into Indigenous health and related training and education continues to increase and diversify. Projects include asthma, bronchiectasis, diabetes in youth, diagnosis of obstetric and paediatric infectious disease and management of cancer in adults.

Above: Risk factor prediction chart for melanoma – a potential new tool for practitioners to advise patients of risk (Source: Whiteman and Green, Cancer Epi Biomarkers Prev 14:761-763, 2005)

Queensland Institute of Medical Research

Genetic Epidemiology Professor Nick Martin Peter Visscher, Andrew Birley, Dale Nyholt David Duffy, Dixie Statham, Margie Wright Michael James, Sue Treloar, Michelle Luciano

The Genetic Epidemiology Group investigates the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems and locate the genes responsible using genetic linkage and association analysis Alcohol consumption is associated with many medical and social variables. With support from both NHMRC and four large new grants from the U.S. National Institute of Alcoholism and Alcohol Abuse, 5,000 pairs of twins plus their relatives have been surveyed, and telephone interviews conducted with over 11,000 twins and 4000 spouses. Genetic factors account for about two thirds of the susceptibility to alcoholism in both women and men in Australia. A major finding is that the aldehyde dehydrogenase gene complex on chromosome 12 has a significant effect on risk of alcoholism and detailed fine mapping of this region will be used to identify causal variants.

In the women’s health area, one project is underway to find the major genes influencing endometriosis and another on super-fertility, as manifested in familial dizygotic twinning. 213 pairs of sisters who each have DZ twins have been genotyped to date with an ultimate sample of 500 planned.

Another focus is the way melanoma runs in families. All familial cases and twins with melanoma diagnosed Queensland Institute of Medical Research

in Queensland and NSW from 19821990 have been identified and are now being followed up in a major NIH funded project which compiles details on sun exposure, natural coloration and moliness in index cases and their relatives.

Much of this year was spent investigating the role of the BRAF gene as a melanoma risk factor.

Moles (melanocytic naevi) are a major risk factor for melanoma and an NHMRC/QCF-funded study is counting and mapping moles in over 1000 pairs of Brisbane 12 year old twins and following them up at their fourteenth birthday. Individual differences in moliness in this sample have been shown to be largely genetic and a recently completed genome scan indicates a number of chromosomal regions of major effect.

Professor Peter Visscher, a leading quantitative geneticist from the University of Edinburgh, and 3 of his PhD students joined the group during the year.

Examples of naevi from a mole study which is contributing to a better understanding of the role of genetic factors in melanoma. Since 1992, 1220 twins and their siblings have been genotyped in the study

Highlights Integrated 4 different genome scans on adult twins and siblings to map genes for blood lead level, cholinesterase and smoking Identified a major gene for migraine on chromosome 5 and others for specific symptoms for migraine elsewhere in the genome Identified a region on chromosome 20 that appears to influence multiple facets of asthma Identified regions for IQ on chromosomes 2 and 6 replicated in an independent study in Holland Showed that the major factor in variation of skin deterioration between people is genetic influences not exposure to sun Identified a significant linkage region for endometriosis on chromosome 20 and a suggestive region on chromosome 20

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Population Studies and Human Genetics Division

Hepatic Fibrosis Associate Professor Grant Ramm Richard Ruddell, Chunxia Xu, Tamara Pereira Marie Bertrand, PengCheng Li, Lyndell Kelly Jeffery Smith, Graeme Macdonald , Peter Lewindon

Investigations in the Hepatic Fibrosis Group centre around the role of liver cells called hepatic stellate cells, in the fibrosis and cirrhosis (liver scar tissue formation), which accompanies serious liver diseases such as the paediatric cholestatic liver diseases biliary atresia and cystic fibrosis and the hereditary iron overload condition, haemochromatosis

Dr Richard Ruddell was awarded the inaugural June W Halliday Young Investigator Award for Science by the Gastroenterological Society of Australia for his work on the role of ferritin in hepatic stellate cell activation and liver scarring

Highlights Identified a panel of serological markers of early hepatic fibrogenesis in patients with cystic fibrosis liver disease Joined a team of investigators awarded an NHMRC Program Grant to study the pathobiological mechanisms of iron-induced cellular and tissue injury in the liver Revealed that the protective bile acid ursodeoxycholic acid is significantly elevated in patients with CF in the absence of liver disease, suggesting the possible existence of an inducible protective mechanism, which fails in some CF patients

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Haemochromatosis and iron-induced hepatic injury This laboratory has a long history of researching the mechanisms of cellular and tissue injury in the liver in the iron overload disease haemochromatosis. The hepatic stellate cell is the principal cell of interest as it is responsible for excess collagen deposition causing scarring of the liver, or fibrosis, in chronic liver diseases. Recently, the laboratory has identified a number of signalling molecules within these stellate cells, which respond to iron-binding proteins interacting with specific binding sites on the cell surface. These signalling molecules appear to be responsible for activating genes involved in inflammation and fibrosis, therefore the current hypothesis is that either iron, or the iron-binding proteins ferritin or transferrin, induce a cascade of signalling events that regulate the phenotype of stellate cells in haemochromatosis. Research is now focused on identifying both external and internal signalling receptor sites in hepatic stellate cells in an attempt to knock out the effects of ferritin and transferrin on stellate cell genes involved in fibrogenesis.

Paediatric Cholestatic Liver Disease Researchers are also working on the potential mechanisms responsible for paediatric cholestatic liver diseases, such as cystic fibrosis and extrahepatic biliary atresia.

In work currently funded by a National Institutes of Health (NIH) grant, a clinical research consortium has been formed with Prof Ross Shepherd, Pediatric Gastroenterology, Washington University, St Louis. This group recently reported that there are clear differences in the serum and biliary bile acid profile in children with liver disease due to cystic fibrosis compared to those children with cystic fibrosis, but no liver disease. Of great interest was the revelation that the protective bile acid ursodeoxycholic acid is significantly elevated in patients with CF in the absence of liver disease, suggesting the possible existence of an inducible protective mechanism, which fails in some CF patients. Current research is now focused on investigating the genetic predisposition of certain patients with CF to develop serious liver disease, well before lung function is diminished.

Queensland Institute of Medical Research

Iron Metabolism Associate Professor Greg Anderson Professor Lawrie Powell, Jeanette Dixon, David Frazer Emily Hay, Kirstin Millard, Therese Murphy Sarah Wilkins

The Iron Metabolism Laboratory focuses on understanding how the essential element iron is transported into and out of cells and how disruption of these processes can lead to human diseases such as haemochromatosis Iron is essential for a large number of critical cellular processes but its concentration in the body must be kept within defined limits. Too little iron can result in anaemia while too much can cause damage to vital organs such as the liver and heart. A central goal of the Iron Metabolism Laboratory is to understand the mechanisms of cellular iron transport and the way in which these processes are regulated. A particular theme is to describe the pathways of intestinal iron absorption and to understand how absorption is altered in disorders of iron metabolism such as haemochromatosis and thalassaemia.

Recent research has been directed towards understanding physiological variations in iron absorption at the molecular level. Situations studied include the modulation of body iron stores, changes in the rate of red cell production, and the acute phase response which is associated with infection and pregnancy. This work has helped define the mechanism by which the liver-derived regulatory peptide hepcidin alters the expression of key iron transport molecules in the intestine, and thus iron absorption, and also how the body directs hepcidin to bring about these effects.

Queensland Institute of Medical Research

A major recent finding of the laboratory is that the enhanced iron absorption associated with the common iron overload disease haemochromatosis results from decreased expression of hepcidin.

However, the anaemia that accompanies inflammation and chronic disease is independent of HFE, indicating that hepcidin expression can be influenced by at least two separate pathways.

Convincing evidence has also been found that hepcidin ultimately responds to the level of differric transferrin in the plasma, the major blood iron transport protein. The Iron Metabolism group maintains a strong interest in iron status in populations with studies on the penetrance of mutations in the gene mutated in haemochromatosis and on the frequency and causes of iron deficiency.

Some pathways of mammalian iron homeostasis

Highlights Showed that hepcidin can be regulated by both HFE dependent and independent pathways Demonstrated that the diferric transferrin in plasma is a major factor regulating hepcidin expression Provided evidence that the increased iron found in patients with advanced liver disease is derived from elevated iron absorption

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Population Studies and Human Genetics Division

Melanoma Genomics Associate Professor Peter Parsons Glen Boyle, Steve Ogbourne, David Chin Julie Pedley, Adam Martyn, Tanya Newton Sarah-Jane Cozzi, Melissa Merritt, Jenny Johns

This group combines expertise in cancer biology with genomics to research communication networks in sun-induced, head, neck and ovarian cancers to address important issues of prevention and treatment The overall theme in this laboratory is to identify and study the function of genes that are important in the development and treatment of certain cancers. Experience gained in melanoma has this year been extended to other tumours such as ovarian cancer, squamous cell carcinoma and breast cancer in respect of genes of interest, and the mechanism of action of a particular class of anti-cancer drug.

Highlights Discovered that ablated expression of genes in human melanoma cells with siRNA technology caused loss of tumourigenicity Identified candidate genes for the prognosis of ovarian cancer from gene expression profiling of tumours and normal tissue Found that human breast and colon cancer cells with high sensitivity to protein kinase C activators are growth-arrested by senescence which may be a novel and non-toxic approach to treatment

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Extensive gene expression profiling within a collaborative NHMRC program has reached the stage of validating gene candidates for the prognosis of ovarian cancer and head and neck cancer. This has entailed extensive laboratory work such as immunohistochemical analysis of tumour sections and data analysis in order to establish correlations between molecular markers and clinical responses.

Several genes are emerging with the potential to predict long term survival after treatment of these serious cancers, a group of patients who cannot otherwise be identified.

This information might also establish gene expression pathways of fundamental significance in tumour development.

In researching genes important in the development of melanoma, several genes in cultured cells have been “knocked out” for the first time and shown that they are no longer tumourigenic in a mouse model.

Anti-cancer compounds from a variety of natural sources are being detected by primary screening, purified and further developed, for several Australian companies.

Above: Expression profiling of ovarian tumors and response to chemotherapy. (a) Dendrogram of chemotherapy response grouping of 737 genes selected using Kruskal-Wallis test (p≤0.05) following hierarchical clustering for visualisation. (b) The expression profiles of the 34 most significantly different genes between non-responders and those that responded with no relapse at 12 months. Blue, non-responders; Green, responders with relapse less than 12 months; Red, responders with no relapse at 12 months.

Queensland Institute of Medical Research

Molecular Epidemiology Dr Grant Montgomery Zhen Zhen Zhao, Anjali Henders, Megan Campbell Lien Le, Christina d’Amato, Leanne McNeill Renee Mayne, Shane Thomas, Steve Crooks

The Molecular Epidemiology Group investigates the pattern of disease in families using high throughput genomic platforms for DNA analysis This group combines research on major projects such as the genetics of endometriosis, dz twinning, melanoma, alcohol and drug dependence, with provision of genotyping services such as zygosity testing, microsatellite and SNP genotyping, sample processing and management of the extensive collection of samples held by the Genetic Epidemiology and Molecular Epidemiology Laboratories.

contributions from family history and maternal age. Finding the gene/s responsible for twinning is likely to provide fundamental insights into mechanisms of female fertility and may have practical implications for controlling fertility and infertility.

One study is recruiting five hundred pairs of sisters from Australia and five hundred pairs of sisters from the Netherlands to undertake a genome scan in these families.

One of the aims of the laboratory is to identify genes that influence women’s susceptibility to endometriosis and understand the pathways to the disease. In collaboration with Dr Sue Treloar and Professor Nick Martin, the largest international collection of affected sister pair families and triad families has been assembled, including 3,900 women with clinically diagnosed endometriosis. Significant linkage to one chromosomal region has been identified. The Sequenom MassARRAY genomics platform is being used to genotype markers in genes under the linkage peak to find the gene or genes predisposing to endometriosis.

The laboratory supports a range of studies in the Genetic Epidemiology laboratory by processing blood samples and extracting DNA. A large inventory of samples is maintained, and samples for genome scans at a variety of sites and for SNP genotyping on the Sequenom MassARRAY genomics platform are prepared and dispatched.

Microsatellite marker analysis are also conducted on an ABI 377 to confirm the zygosity of twins in a range of studies.

The tendency to conceive spontaneous dizygotic twins is a complex trait influenced by genetic and environmental factors with Queensland Institute of Medical Research

During the year, Dr Penelope Lind joined the group as a Research Officer from the University of North Carolina at Chapel Hill. With a primary interest is in alcohol addiction, Dr Lind will coordinate candidate gene SNP typing for our alcohol-related Interactive Research Project Grants.

Steven Crooks checking DNA sample IDs

Highlights Identified a heterozygous deletion in GDF9 in sisters with dizygotic twins. GDF9 is an important intra-ovarian growth factor and mutations in GDF9 increase twinning in other species Completed genome scans in adolescent and adults twin cohorts and analysed these to locate gene regions predisposing to melanoma, blood cell phenotypes and smoking Conducted a pilot project with the AGRF on the Affymetrix GeneChip® SNP genotyping platform. Analysis of 60,000 SNPs demonstrated very low error rates for high quality DNA samples Failed to replicate previous findings of an association between the progesterone receptor and endometriosis in a large family collection

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Indigenous Health Research Program

This program carries out collaborative research projects for the improvement of the health and well being of Aboriginal and Torres Strait Islander peoples The Indigenous Health Program has continued to grow with an increase in students and collaborative projects. Simõne Smith, the Program’s first Honors student who is working in the Clinical Tropical Medicine laboratory began this year, along with Lisa Whop, first National Indigenous Cadetship Project participant who is enrolled in a Bachelor of Applied Science (Medical Science) at QUT and will carry out her work placement with Scientific Services. Both Simõne and Lisa are supported by the Cooperative Research Centre for Aboriginal Health (CRCAH) in terms of scholarship and work placement respectively.

Karen Taylor is close to completing her Masters of Applied Research (Science) project ‘Give your baby a better chance; innovative testing prior to birth’, funded by CRCAH. Aletia Twist is now working as a Senior Public Health Nutritionist in Cairns and has changed her PhD enrolment to part time for her project on obesity and Type 2 diabetes in the Torres Strait.

A new Indigenous staff member Vanessa Clements, whose position is funded through ACITHN, joined the team this year. Vanessa is working as a project officer and brings to the program valued expertise from her previous work as an Aboriginal Health Worker.

Top: Ida Savage, a local health worker in the project which evaluated an education intervention program for childhood asthma by Aboriginal and Torres Strait Islander health workers Below: Simõne Smith, Indigenous Program Honours student working in the Clinical Tropical Medicine laboratory

The Spotlighting Careers in Indigenous Health and Science Program was held again this year with student numbers increasing from eight to twelve. The Indigenous and non-Indigenous year 11 students from Far North Queensland, accompanied by two science teachers, spent three days working in QIMR laboratories. They also visited The University of Queensland Indigenous Health Division and the Queensland University of Technology to learn about undergraduate courses, Southbank and the Queensland Museum. Feedback from the students was very positive with all reporting it was a great chance to experience real science and do things they would never be able to do at school.

The cancer in Aboriginal and Torres Strait Islander People in Queensland project, conducted in collaboration with Queensland Health, has now been completed and findings will be published later this year. Detailed data on cancer in Indigenous people have only been published for SA, WA and NT. The first population-based comparative study of cancer in Indigenous and non-Indigenous patients in Queensland, in particular exploring cancer stage at diagnosis and co-morbidities, has also been completed. This study is seen as a first step in understanding the problem with much more knowledge needed in order to improve the situation. Findings will be presented and the possibility of further culturally respectful research projects discussed with representatives from health service delivery and the Aboriginal and Torres Strait Island Community.

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Queensland Institute of Medical Research

Ms Janelle Stirling Patricia Valery, Vanessa Clements, Veronica Harrhy

The work of the Malaria and Scabies, Bacterial Pathogenesis, Clinical Tropical Medicine and Molecular Immunology laboratories on improved treatment and prevention for scabies and vaccine development for Group A Streptococcus is continuing with its major funding from NHMRC, NIH and NHF. A small trial of the Wuchopperen skin study has been completed and outcomes are currently being analysed.

High school students taking part in the Spotlighting Careers in Indigenous Health and Science Program

A project evaluating an education intervention program for childhood asthma

by Aboriginal and Torres Strait Islander Health Workers commenced field work in April 2005. This is a collaborative project with the Thursday Island Primary Health Care Centre, the Asthma Foundation of Queensland and The Royal Children’s Hospital. During a first visit to Thursday Island, a three day Health Worker training course ‘Recognising and helping children with asthma in the Torres communities’ was conducted and attended by eleven local Health workers. Ninety children and young people visited the pediatric respiratory clinics conducted by Dr Brent Masters and Dr Anne Chang. From this group 18 were identified as suitable for inclusion in the intervention group. Local health workers are now conducting follow up visits with the intervention group in the hopes of showing an improvement in asthma management for this group.

Work on the multi-centre bronchiectasis observational study, which is part of a collaborative and international study of bronchiectasis in Indigenous children is continuing. The study site for this project in Australia is the Northern Territory.

Mr Michael Gooda, CEO for the CRCAH, addressed the Program’s anniversary seminar this year, sharing his insights into ‘Contradictions, confusion and Ironies in Aboriginal Affairs’.

In recent times the CRCAH board has been refining the research agenda and has made some changes in staff and management processes. The Board is pleased with the progress made by the CRCAH under Michael Gooda’s leadership and are currently negotiating for additional funding to support the work on scabies and Group A Streptococcus which fits into the healthy skin program. The Indigenous cancer project is also an in-kind project with the CRCAH. The team looks forward to another productive year with the prospect of more publications from the program in the near future and further success in grant applications.

Queensland Institute of Medical Research

Highlights Completed data analysis for cancer in Aboriginal and Torres Strait Islander people Dr Patricia Valery awarded Telstra Foundation grant for Bronchiectasis Observational Study Project team which conducted an evaluation of an education intervention program for childhood asthma by Aboriginal and Torres Strait Islander Health Workers awarded Royal Children’s Hospital Foundation Grant Signed a Memorandum of Understanding between Queensland Health and the Queensland Institute of Medical Research via the Indigenous Health Research Program

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Therapeutic Development and Clinical Research Division

The Therapeutic Development and Clinical Research Division is committed to the development and testing of immunotherapeutics manufactured within the Q-Gen laboratories. Included in the Division are the EBV Biology, Cancer Immunotherapy, and Tumour Immunology laboratories. Currently, six cellular based vaccine trials are being undertaken or planned to commence shortly. These trials are aimed at testing cell-based therapeutics to cure post-transplant lymphoma, Hodgkin’s disease, malignant melanoma, prostate cancer and cytomegalovirus infection.

Five of the trials are phase I and one of the trials is a phase III trial on melanoma patients with minimal metastatic deposits. The Phase III trial is very important in the Division’s focus since it was initiated on the basis of promising results from a phase I/II trial. The Q-Gen facility has a licence from the Therapeutic Goods Administration (TGA) to manufacture products to Good Manufacturing Practice (GMP) standard for the Phase III trial.

It is important to point out that clinical trials conducted within the Division frequently become the focus for additional basic research. For example, the question of why some patients respond to cell-based therapy while others do not, opens up the scientific issue of defining the components of the immune system responsible for protection from cancer. This illustrates the concept that the Division aims to take laboratory-based research from the laboratory into the clinic and subsequently back into the laboratory, a cycle which should eventually result in the development of immune-based therapies that are capable of resolving disease.

Details of clinical trials currently underway are listed on the following page.

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Queensland Institute of Medical Research

QIMR sponsored clinical trials during 2004-2005

Chair – Professor Denis Moss

CLINICAL TRIAL

INVESTIGATORS

Prostate cancer: An internal solidmalignancy model for vaccine therapy (NUQM00J1)

Investigators: Prof Kay Ellem, Dr Christopher Schmidt, Atlantic Philanthropies: Dr Bev Kerr, Mrs Linda O’Connor, $11,000 Mrs Cathy Davern (QIMR), Prof Frank Gardiner, Philanthropic sources: $45,000 Mrs Betty Scells, Ms Liz Hamlyn (The University of Queensland, Royal Brisbane Hospital), Prof Greg Seymour (The University of Queensland), Prof Derek Hart (Mater Medical Research Institute), Dr David Yaxley, Dr David Nicol (Urological Society of Australasia).

Phase III trial of an immunotherapy for Stage III (AJCC) melanoma based on cultured autologous dendritic cells presenting autologous tumor cell antigens (MRPQ0161)

Investigators: Prof Kay Ellem, Dr Christopher Schmidt (QIMR), Prof Michael O’Rourke (Mater Adult Hospital), Dr Barry O’Loughlin (Royal Brisbane Hospital), A/Prof Mark Smithers (Princess Alexandra Hospital), Dr David Ritchie (Malaghan Institute, New Zealand)

Phase I trial of the safety, the effect on immune parameters, and clinical efficacy of an immunotherapy for glioma, based on cultured autologous dendritic cells presenting autologous tumour antigens (RMQ0331)

Investigators: Dr Christopher Schmidt, Prof Kay Ellem RBWH Foundation: $20,000 (QIMR), Drs Richard Laherty, David Walker and Frank Viertel Fellowship: $30,00 Tomlinson (Royal Brisbane Hospital), Prof Michael O’Rourke (Mater Adult Hospital)

Dendritic cell vaccination trial for hormone refractory prostate cancer with autologous tumour as the antigen (NRQ03J1)

Investigators: Prof Kay Ellem, Dr Christopher Schmidt, Atlantic Philanthropies: Prof Martin Lavin (The University of Queensland), Dr $11,000 Michelle Burger, Ms Linda O’Connor (QIMR), Prof Philanthropic sources: $45,000 Frank Gardiner (University of Queensland, Royal Brisbane Hospital)

Adoptive immunotherapy for the prevention of human cytomegalovirus (HVMV) reactivation and disease after allogeneic stem cell transplantation (QR-2002-CMV1)

Investigators: Dr Rajiv Khanna (QIMR), Dr Geoff Hill (QIMR, Royal Brisbane Hospital), Drs Simon Durant, James Morton (Royal Brisbane Hospital), Dr Leanne Lockwood (Royal Children’s Hospital), Dr Suzanne Elliott (Q-Pharm)

Queensland Institute of Medical Research

FUNDING

Atlantic Philanthropies: $100,000 Clive Berghofer Fund: $250,000 NHMRC: $55,000

Queensland Leukaemia Foundation: $100,000

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Therapeutic Development and Clinical Research Division

Translational Research Dr Geoff Beadle Sandra Stein, Toni Jones, Donna Spooner Katharine Kennedy

The goal of the Translational Research laboratory is to foster research collaborations between scientists and clinicians for the beneďŹ t of patients and society

HER 2 over-expression in breast cancer using chromogenic in situ hybridisation

Highlight A project evaluating the impact of chemotherapy on cognitive functioning in women with breast cancer continued to attract participants to become the second largest longitudinal study in the world

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The Translational Research laboratory continues to build its activities principally around breast cancer research and currently holds almost 900 breast cancer pathology specimens with ethics approvals. These specimens have been fully characterised in terms of known clinical prognostic factors, and patient outcomes are known.

Currently available biomarkers are being assessed on this database to determine their relevance as predictors of patient outcomes. In addition, the laboratory is extending this pathology database to more than 1500 samples. When complete, this expanded pathology database will provide an important basis for exploring novel genes involved in breast cancer behaviour.

with breast cancer immediately after diagnosis and before chemotherapy starts. The project continues to attract participants at a steady rate and is now the second largest longitudinal study in the world.

Preliminary results conďŹ rm that the cognitive tasks selected for this study can identify subtle but deďŹ nite differences in cognitive functioning immediately after completion of chemotherapy. This project will continue to recruit women with early breast cancer over the next year and preliminary results of long term effects of chemotherapy on cognitive functioning will be available in the next 2 years.

The second major project is evaluating the impact of chemotherapy on cognitive functioning on women with breast cancer. To date, most studies in this emerging area of research have demonstrated measurable but minor impairments during and after treatment with chemotherapy.

Interpretation of these studies has been hampered by their design.

The current study is undertaking the important step in assessing cognitive functioning of women Queensland Institute of Medical Research

Joint Programs

Australian Centre for International and Tropical Health and Nutrition A joint venture with The University of Queensland

In 2004, considerable efforts were expended in preparing submissions for a review of the third Public Health Education and Research Program cycle. Submissions were prepared by QIMR, the School of Population Health at The University of Queensland, the Centre for Indigenous Health and the Australian Network of Academic Public Health Institutions. These were considered, amongst many others, by a steering committee convened by the Australian Government Department of Health and Ageing.

The Australian Centre for International and Tropical Health and Nutrition (ACITHN) objectives were outlined as developed in a 1995 contract with the Australian Government which formally designated ACITHN as a national centre. In today’s national and regional context, these objectives are considered more important than ever. Mainly based on evidence already provided in annual reporting documents and ACITHN Annual Reports, it was argued that ACITHN is a valuable and cost-effective resource for public health workforce development, research training and strategic research, and one which created leverage of 6.8 times the governmental contribution in 20042005. A great strength of ACITHN is in outreach activities via numerous collaborations with scientists and educators in 26 countries, and its strong contribution to policy development through numerous memberships on expert panels and committees.

Queensland Institute of Medical Research

The submission outlined some future directions for ACITHN and signalled a broadening of interest to include priority setting and policy development, and the development of interventions for both communicable and noncommunicable diseases. A strategic approach was suggested that might enhance working alliances with key regional groups including WHO/ WPRO, SEAMEO TROPMED and the Australian Biosecurity CRC for Emerging Infectious Disease.

During July 2004, ACITHN convened the Asia-Pacific Forum on Tropical Health Innovation with major sponsorship from the Qld Department of State Development and Innovation to link public health, biotechnology and information technology with other sectors such as the Armed Services, travel and tourism. The Forum will not only enhance capacity to deal with biosecurity and communicable diseases threats, but also assist in building economies by creating healthy destinations. In particular, this initiative which engaged the travel and tourism industry was stimulated by the appearance of SARS and Avian Influenza.

Effective Australian public health will be better served by taking an Asia-Pacific perspective in terms of networking, surveillance and intervention. It is crucial that a capable workforce is fostered to carry out such tasks and develop dialogues with other interest groups.

During May 2005 when the federal budget was announced, the Public Health, Education and Research Program was included for renewal but at this stage, ACITHN awaits information from the Australian Government as to the actual format for the fourth cycle and confirmation of the directions it has nominated for the betterment of public health.

Above: Professor Brian Kay, Director of ACITHN, and Linda Larvich representing Tony McGrady at the Asia Pacific Forum Below: Professor Brian Kay presenting Madga Ellis with the student prize at the Asia-Pacific Forum

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Joint Programs

Cooperative Research Centre for Vaccine Technology

The Cooperative Research Centre for Vaccine Technology (CRC-VT) is a joint venture of eight organisations: the Queensland Institute of Medical Research, The Walter and Eliza Hall Institute of Medical Research, The University of Melbourne, Monash University, La Trobe University, CSIRO Division of Livestock Industries, the Australian Red Cross Blood Service (ARCBS) and CSL Limited With the support of a major grant from the Australian Government’s Cooperative Research Centres Program and cash and in-kind contributions from the joint venture partners, scientists in each of the partner organisations work together to create and develop new prototype vaccines, vaccine platform technologies and immunotherapeutic agents for the improvement of human and animal health.

PhD students from the CRC-VT and other Brisbane CRCs taking part in a student retreat that focused on managing people and career development

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In its last year of full Commonwealth funding, the CRC-VT focused research spending on six projects that show potential to be ready for commercialisation before the Centre grant ends in mid-2006.

Two of those projects were led by Dr Rajiv Khanna at QIMR, one to develop a vaccine against human cytomegalovirus (HCMV) and the other to measure HCMV-specific T cell responses in transplant patients at the Princess Alexandra and Prince Charles Hospitals in Brisbane.

Another QIMR-based project was led

by Professor Denis Moss and is part of a major effort to develop a vaccine against the Epstein-Barr virus-related cancer nasopharyngeal carcinoma.

Other CRC-VT projects continued development of human plasmaderived mannose binding lectin as a potential therapeutic agent, design of self-adjuvanting protein vaccines and testing of novel approaches to the induction of mucosal immunity.

The Centre now holds a substantial intellectual property (IP) portfolio in the fields of vaccines and immunotherapeutics. Negotiations for the commercial development of a number of patent-protected technologies were well advanced at the end of the year. A major strategic undertaking during the year was the analysis of pathways to manage CRC-VT IP and commercial agreements after the Centre

completes work in mid-2006. By June 2005, implementation of the selected pathway was well advanced and should ensure that the long-term benefits of the Centre’s IP can be fully realised through commercial development and continued research in publicly-funded partnerships.

The CRC-VT continues to support a strong education program and is on track to see the completion of about 70 PhD students enrolled since 1993. In addition to undertaking very high quality research through their host institutions, CRC-VT students are exposed to training in various aspects of IP protection and commercialisation. During the year, several students undertook a CRC-VT-funded 2 to 3 month industry sabbatical at CSL or GlaxoSmithKline, in two cases leading to employment by the host company. In 2005, the CRC-VT also provided a retreat at the Bardon Centre in Brisbane for students from our Centre and two other Brisbanebased CRCs to learn about managing people and career development.

The Centre’s contribution to the professional development of new researchers in the vaccine field is likely to have a lasting impact, as equally important as the commercial and other outcomes of its research activities.

Queensland Institute of Medical Research

Spin-Off Companies

Q-Pharm Pty Ltd Q-Pharm concluded its third full year of trading as a private company on 30 June 2005 with 2004-2005 proving a very satisfactory year. Highlights of the year include: • Gross revenue from operations increased by 50% from 2003-2004 levels and profitability improved substantially

The Q-Pharm open plan clinical trials ward

• Growth occurred in all areas of the business but most importantly in the Phase I/II clinical trials area which has seen a 200% increase in revenue and in the bioequivalence study area which remains a very strong contributor to the company’s operations • Broadening of the client base in accordance with the business plan, predominantly from overseas clients and major pharmaceutical companies • Being named as an industry partner in a successful Pharmaceuticals Partnership Program grant, an outcome that should see at least a doubling in the volume of work from this client in the future

The Q-Pharm bioanalytical laboratory

• Purchase of an API4000 liquid chromatograph/tandem mass spectrometer that will significantly increase analytical capability • Healthy employment growth continued at Q-Pharm which now supports 45 full-time equivalent positions

Q-Gen Pty Ltd In September 2004, QIMR created Q-Gen Pty Ltd as its commercial arm for contract manufacture of therapeutics. There has been considerable national and international interest in the commercial and academic provision of contract manufacturing services. Q-Gen Pty Ltd will offer contract production for cellular therapies including gene therapy, dendritic therapies, adoptive immunotherapy, somatic cell therapy and stem cell therapies. Additionally Q-Gen Pty Ltd has a fermentation and cell culture suite for the production of biologics up to 50L capacity. Stability trials for therapeutics will be offered and can be facilitated at a range of temperatures and time courses. The facility provides manufacturing areas which can be used for sterile manufacture, formulation, fill and finish for liquid dosages.

Q-Gen Pty Ltd runs an ISO 9001:2000 based Quality System for all of its products. The Q-Gen team has been through four multiple day audits by the Australian Therapeutics Goods Administration (TGA) and are confident in their ability to provide comprehensive services to external as well as internal (QIMR) clients.

Top: Dr Ming Lin calibrates pipette prior to using it in analytical assay Below: Dr Silvana Sekulowski bioprocess monitoring

Queensland Institute of Medical Research

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Spin-Off Companies

Vaccine Solutions

Vaccine Solutions CEO, Beryl Morris, took Vaccine Solutions to the 2004 Bio Japan Expo in September

QIMR is a 50% shareholder of Vaccine Solutions, a technology commercialisation company which was founded in 1997 to provide services to the Cooperative Research Centre for Vaccine Technology (CRC-VT), of which QIMR is a party. This year, Vaccine Solutions managed 20 patent families and in-licensed six technologies from the CRC-VT. The company has already negotiated deals to out-license five of its technologies. Two of these are related to inventions QIMR has contributed to the CRC-VT, diagnostic use of human cytomegalovirus epitopes and a polyepitope vaccine for use against EBV-related nasopharyngeal carcinoma. As part of its preparations for the end of the CRC-VT in June 2006, Vaccine Solutions transferred to QIMR two major malaria vaccine research and development contracts. These contracts are with the Seattle-based Program for Appropriate Technologies in Health (PATH) Malaria Vaccine Initiative (MVI).

Replikun Biotech Pty Ltd Replikun Biotech Pty Ltd is a biotechnology company formed by QIMR in March 2005 to commercialise a novel, potent vector delivery system (KUNrep™). The KUNrep™ systems are derived from Kunjin virus, an Australian native flavivirus. Start-up funding of $1.875 million was raised from Start-Up Australia to support the first phases of development.

Replikun has an exclusive, worldwide licence to commercialise the technology with a portfolio of issued patents and pending patent applications that protect the KUNrep™ vectors, their means of production, modes of delivery and therapeutic applications.

There is a large, unmet need in the vaccine and gene therapy markets for a safe and robust delivery system. A major objective of the new company is for its technology to become the method of choice for delivering antigens or genes to patients, thus creating valuable medical products. Replikun will create value by partnering with biopharmaceutical companies and incorporating their gene/antigen into the KUNrep™ systems.

Adipogen Pty Ltd Adipogen Pty Ltd is a spin-off company of the University of Queensland that has licensed intellectual property developed by Professor John Prins. The company is developing products to assist in the treatment of obesity.

The Queensland Institute of Medical Research holds equity in Adipogen Pty Ltd on behalf of Queensland Health.

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Queensland Institute of Medical Research

Corporate Division Michael Staley – Chief Operating Officer

QIMR has more than doubled in size and research activity since 1999.

The world-class research carried out by the Institute’s scientists requires high quality scientific and administrative support. The Corporate Division provides this support through departments covering finance and administration, human resources, scientific services, information technology, building services, regulatory affairs, business development and safety.

This last year has seen a further development and implementation of systems for financial and human resource services. During the 2004-2005 year, the Finance team commissioned a new grants management system and Human Resources implemented a new performance appraisal system for general staff.

Information Technology has managed significant infrastructure expansion to accommodate an ever increasing volume of scientific data. A major upgrade of network cabling in the Bancroft Centre provided faster network access for staff and mission critical E-forms system, which is used for electronic submission of Ethics and Safety proposals.

QIMR’s Virtual Private Network (VPN) has become an extremely useful tool for staff requiring remote access to the network. The recent installation of a state of the art video-conferencing system was also successful. With connections via ISDN and/or the Internet, the system was recently used to allow Queensland high schools to participate in the Institute’s annual High School Science Lecture series.

The Business Development office has the primary responsibility of protecting and commercialising QIMR’s intellectual property, which is generated by QIMR’s scientists. A successful example of this during 2004-2005 was the formation of the spin-out company, Replikun Biotech Pty Ltd (Replikun).

The company was formed by QIMR to further develop and commercialise technology applications of the Australian Flavivirus, Kunjin. This technology has been developed over several years by scientists at the Department of Health Services, The University of Queensland and QIMR for new medical uses for the Kunjin virus.

Alan Stockman Building Services Tracey Mynott Business Development Marlene Cornell Finance Nicole Green Human Resources Chris Ward Information Technology Agnieszka Mitchell Regulatory Affairs Juan Cooper Scientific Services Helen Leonard Workplace Health and Safety

In Scientific Services, this past year has seen considerable planning for redevelopment of the animal facility to increase animal holding space whilst providing a safe environment for both animals and staff. After extensive consultation with architects, researchers and the QIMR Animal Ethics Committee, the design development phase was completed early in 2005.

Construction of a new experimental holding area and support areas began in June with expected transfer of animal operations in October 2005.

Refurbishment of the facility is eagerly awaited by scientists and support staff.

Queensland Institute of Medical Research

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Corporate Division

To maintain up to date knowledge of the ethical and regulatory framework, QIMR Human Research Ethics Committee (HHREC) members attended an NHMRC Research Ethics Training Sessions in Brisbane in August 2004 and the NHMRC Research Ethics Conference in Canberra in May 2005. The HREC Chair provided a written submission to AHEC on behalf of the HREC regarding the revision of the National Statement on Ethical Conduct in Research Involving Humans.

The Safety team managed the compliance of more than 600 projects for chemical risk and biosafety. In addition, there are 107 users of isotopes within QIMR, and the Radiation Safety OfďŹ cer examines 25-30 protocols a year for compliance. Staff training and education is a high priority and each year all staff attend workplace health and safety and ďŹ re safety training seminars. The Safety Committee oversaw all aspects of safety at QIMR during the year.

Building Services maintain the facilities at QIMR and are responsible for the security of many systems and services which are mission-critical to the research program. They provide a 24 hour service to ensure that essential systems are maintained and this year, have been actively involved in planning for the refurbishment of level G of the Bancroft Centre and Level C of the Clive Berghofer Cancer Research Centre.

Right: The Clive Berghofer Cancer Research Centre

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Queensland Institute of Medical Research

Queensland Institute of Medical Research

65

Official Committees 2004–2005

QIMR COUNCIL Sir Bruce Watson (Chair) Mr Paul Wright (Deputy Chair) Dr Paul Bartley (to June 05) Prof Bryan Campbell Prof Peter Brooks Mr Christopher Coyne (from June 05) Prof Judith Clements Ms Clare Endicott (to June 05) Mr Paul Fennelly Dr Gerry FitzGerald Prof Lyn Griffiths Prof Alan Lopez (from June 05) Prof Brandon Wainwright (to June 05) Committees reporting to Council: Appointments & Promotions Committee Prof Peter Brooks (Chair) Prof Graham Brown Prof Julie Campbell Prof Judith Clements Dr Andrew Cuthbertson Dr Gerry FitzGerald Prof Lyn Griffiths Prof Alan Lopez (from June 05) Prof James McCluskey Prof Joe Trapani (from June 05) Prof Brandon Wainwright (to June 05) Prof Michael Good (ex officio) Animal Ethics Committee (AEC) - AEC Scientific Sub-Committee Finance & Audit Committee Mr Paul Wright (Chair from June 05) Dr Paul Bartley (to June 05) Prof Bryan Campbell (from June 05) Dr Gerry FitzGerald Mr Bruce Phillips (from June 05) Sir Bruce Watson (Chair to June 05) Mr Rod Wylie

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Human Research Ethics Committee (HREC) - HREC Scientific Sub-Committee Dr Greg Anderson (Chair) Dr Christian Engwerda Dr Kevin Spring Ms Carmel Kerwick Dr Douglas Lincoln Dr Don Gardiner Dr Colleen Olive Mrs Sue Cassidy Dr Agnieszka Mitchell Dr Helen Leonard Ms Jo Chow - Secretary - HREC Clinical Trial Protocol Sub-Committee Dr Peter Roeser (Chair) Dr Agnieszka Mitchell Prof Andrew Boyd Dr Suzanne Elliott Dr Greg Lawrence Dr Douglas Lincoln Dr Christopher Schmidt Dr Lesley Ross-Lee Dr Geoff Beadle Ms Alyce Maksoud Dr Jason Lickliter Ms Jo Chow - Secretary Personnel Administration Committee Sir Bruce Watson (Chair) Ms Clare Endicott (to June 05) Dr Gerry FitzGerald Mr Rod Wylie (from June 05) Mr Paul Wright Committees reporting to the Director: Management Executive Committee Prof Michael Good (Chair) Prof Adèle Green Prof Andrew Boyd Prof Martin Lavin

Prof Denis Moss Mr Michael Staley Dr Kum Kum Khanna Dr James McCarthy Dr Greg Anderson Ms Janelle Stirling Ms Nerida Fox – Secretary Biosafety Committee Dr Helen Leonard (Chair) Dr David Tscharke (Deputy Chair) A/Prof Peter Upcrofe Mr Paul Collins Dr Juan Cooper Dr Therese Murphy Mr Michael Staley Mr Alan Stockman Dr Christine Rzepczyk Mr Andrew King Prof Denis Moss Dr Greg Lawrence Dr Michael Batzloff Dr Glen Boyle Mr Ron Buttenshaw Ms Jo Chow - Secretary Equipment Committee Prof Andrew Boyd (Chair) Dr Juan Cooper Dr Kum Kum Khanna Dr James McCarthy Prof Denis Moss Ms Alison McLean Mr Chris Ward Higher Degrees Committee Dr Tom Sculley (Chair) Prof Michael Good Dr Graham Kay Dr Nathan Subramaniam A/Prof Andreas Suhrbier A/Prof Alan Lawson A/Prof Peter O’Rourke Dr Judith Greer Dr Peter Ryan Queensland Institute of Medical Research

Dr Jackie Upcroft Dr Katherine Trenholme Dr Sue Treloar - Secretary Mrs Simone Cross Ms Janelle Stirling Ms Sarah-Jane Cozzi Ms Lynette Beattie Ms Jyoti Jonnalagadda Joint Consultative Committee Ms Nicole Green (Chair) Dr Grant Ramm Dr Penny Webb Prof Michael Good Mr Michael Staley Dr Kum Kum Khanna Mr Rick Woods Mr Paul Collins Ms Pauline Donnelly QPSU Representative QNU Representative Medical Advisory Board Prof Peter Brooks (Chair) Prof Andrew Boyd (Deputy Chair) Dr Paul Bartley Dr Geoff Beadle Dr Ian Bunce Dr Don Cameron Prof Adèle Green Prof Michael Good Dr Barbara Leggett Dr Joseph McCormack Dr Paul Sandstrom Dr Mark Smithers Dr John Varghese Dr Michael O’Rourke

Queensland Institute of Medical Research

Mentoring Committee Dr Grant Ramm (Chair) Dr David Whiteman Dr Nick Hayward Dr Georgia Chenevix-Trench Dr Rajiv Khanna Scientific Advisory Board Prof Graham Brown (Chair) Prof Beth Newman Prof Nicos Nicola Prof Joe Trapani Seminars Committee Prof Michael Good (Chair) Dr Grant Montgomery Prof Martin Lavin Dr Kate Green (to Dec 04) Dr Katharine Trenholme Ms Rosemary Lynch (to Feb 05) Ms Jann O’Keefe (from Mar 05) Committees reporting to the Chief Operating Officer: Commercialisation Committee Dr Tracey Mynott (Chair) Dr Kate Andrews Dr Mark Egerton Mr Michael Staley Prof Andrew Boyd Prof Dave Kemp A/Prof Andreas Suhrbier IT Committee Dr Tom Sculley (Chair) Mr Christopher Ward Mr Michael Staley Dr Scott Burrows Mr Mark Feodoroff Ms Michelle Gatton Ms Heather Matthews Ms Nirmala Pandeya Prof Peter Upcroft Dr Nathan Subramaniam

Dr David Smyth Dr Glen Boyle Mr Mark Spanevello Dr Nuri Gueven Dr Agnieszka Mitchell Dr Juan Cooper Ms Jann O’Keefe (from Mar 03) Library Committee Mr Christopher Ward (Chair) Prof Michael Good Mr Michael Staley Dr Greg Anderson Prof Andrew Boyd Dr David Whiteman Ms Jennifer Ho Dr Lihua Zhang Prof Dave Kemp Dr Rajiv Khanna QIMR TRUST Mr Paul Wright (Chair) Mr John Garnsey Mr Ian Manly Mr Rod Wylie Mr Richard Joel Mr Bruce Phillips Ms Margot de Groot Ms Patricia McCormack Ms Jane Seawright Committees reporting to Trust: Trust Investment Committee Mr Rod Wylie (Chair) Mr Paul Wright Mr Ian Manly Mr Bruce Phillips Trust Marketing Committee Mr John Garnsey Ms Margot de Groot Ms Jane Seawright

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Development and Marketing

The Development and Marketing Department was established in 1994 to raise public awareness and funds for QIMR. The Department is responsible for many activities including fund raising events, bequests, news releases, media liaison, newsletters, fact sheets, brochures, powerpoint presentations and public awareness campaigns.

Below: Cyclists in the Suncorp Ride for Research, an event which raised significant funds for skin cancer research at QIMR, and included a number of keen QIMR cyclists, shown above

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Tours of QIMR and external speaking engagements are also organised by the Department. Many of these are arranged by groups such as National Seniors Associations, Probus, the Association of Independent Retirees and church groups. Since 1995, the number and size of tours and speaking engagements has expanded enormously, and this year, more than 8,000 people learned more about vital medical research and how this impacts on health, life and longevity.

The Department has built numerous beneficial relationships with individuals and companies such as Clive Berghofer, Suncorp, Sam Coco, AMAQ VMO Committee, ABC Learning Centres, Callaway Golf HiLite Pro Am, the Pratt Foundation, Queensland Property Foundation, the Wantz Committee and many others whose names are listed in the Donors section on pages 94–99.

One of the fundamental activities of the Department is to disseminate research findings to the community and, as QIMR has no budget for advertising, this is done through

no-cost releases circulated regularly to the Australian media. Media coverage received as a result of these releases has more than tripled over the past seven years.

The quarterly newsletter, Lifelab, is vital in communicating QIMR research to the public and also generates significant donations to ensure that life-saving medical research continues. The amount of donations received following from Lifelab mailouts increases steadily, and has also tripled in over the same seven year period.

THANKS TO THE COMMUNITY Many people attend QIMR fundraising events or participate through donations, gifts-in-kind, bequests, sponsorship and through purchasing tables/tickets.

Likewise, many people spread the word about QIMR and its research, results and needs through their networks. For all this support, the Institute is greatly indebted.

Queensland Institute of Medical Research

Training and Education Program

Postgraduate Training at QIMR

This year QIMR admitted 33 new higher degrees students and had 46 visiting students at QIMR. Currently the student body at QIMR comprises 119 PhD, 17 research Masters and 21 Honours students. This indicates that an increasing number of students are turning to the Institute for advanced research training and emphasises the standing of QIMR in the research community. In addition to students working towards degrees, the Institute maintains an active Summer Vacation Scholarship Program and welcomes many work experience students from local high schools. Most QIMR students are enrolled through the University of Queensland, particularly through the School of Population Health and the School of Medicine. An increasing number of students are also coming through other Universities including Griffith University, the Queensland University of Technology and the University of the Sunshine Coast.

Postgraduate students from QIMR continue to make an impact in the wider scientific community, and again this year have received a number of significant accolades.

Some examples include; Michelle Neller who received an award for the best oral presenter for a first year PhD student at the Australian Society for Medical Research during Medical Research Week, while Magda Ellis received the best student poster award at the Asia-Pacific Forum for Tropical Health in Cairns.

Amber Glanfield was also awarded best student poster at the Australian Society for Parasitology Conference Queensland Institute of Medical Research

in Fremantle and Yang Yurong, best oral communication by a student at the XXIst International Congress of Hydatidology, Kenya, 2004.

The Higher Degrees Committee (HDC) continues to oversee student activities at QIMR. Committee duties include the evaluation of students prior to their acceptance as candidates at the Institute, monitoring student progress, providing education programs for students, establishing policy on issues relating to students, and assessing applicants for travel awards, Honours scholarships and PhD top-up scholarships. Increasing emphasis on the timely completion of research degrees has meant that the monitoring of student progress is becoming an ever more important activity and members of the HDC devote considerable time to the rigorous review of students during their study program. This year the committee undertook 58 reviews of students.

A new QIMR Student Club has organised various social functions to unify the larger numbers of students in both buildings of QIMR. Student Club committee members and the HDC student representatives are combining efforts to organise the next Student Retreat to be held in November 2005.

QIMR offers an outstanding environment for advanced training in biomedical research at an international level through the excellence of its scientists, its wide network of research collaboration both nationally and internationally, as well as world-class facilities and support services. Postgraduate students represent a valuable part of the research activities at QIMR, and the Institute seeks to provide them with a solid grounding in medical research for subsequent careers either in Australia or abroad.

Because the quality of supervision has a major impact on the quality of the students produced, the Institute conducts a two-part workshop for supervisors of postgraduate students in conjunction with the Teaching and Educational Development Institute and the School of Population Health of the University of Queensland. QIMR will continue to promote itself as a centre of excellence for postgraduate training in Australia.

QIMR Students at the Asia-Pacific Forum for Tropical Health held in Cairns

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Training and Education Program

Completed Students 2004–2005

Student Name

University/Supervisors

Thesis Title

I Anraku

School of Population Health, UQ Andreas Surhbier, Alexander Khromykh

Induction of long lasting protective CD*+T lymphocyte responses by Kunjun replicon-based vaccine vectors

P Bartley

School of Population Health, UQ Don McManus

Artemether and the immunobiology of Schistosomiasis japonica

A Boyd

School of Population Health, UQ Brian Kay, Roy Hall

Interactions between common vertebrate hosts and the mosquito vectors of Ross River and Barmah Forest viruses in urban Brisbane, southeast Queensland

T Cook

Institute of Molecular Biology, UQ Rick Stern, Helen Leonard

Models of human neural crest cell differentiation in vitro

S Cozzi

Physiology and Pharmacology, UQ Peter Parsons

Molecular targets of anti-cancer PKC activators in the treatment of melanoma

S Duffy

School of Medicine, UQ Andrew Boyd, Joe Rothnagel

The role of the EphA1 receptor tyrosine kinase during embryogenesis and cancer

G Darnell

School of Population Health, UQ Andreas Surhbier, Toni Antalis

A novel intracellular activity for the serpin PAI-2

X Huang

School of Medicine,UQ Kay Ellem, Chris Schmidt

Depot cytokines and chemokines for anti-tumour therapy in a mouse model

L Hugo

School of Population Health, UQ Peter Ryan, Brian Kay, Scott O’Neill

Evaluation of methodologies for determining the age structure and survivorship of Ochlerotatus vigilax and other important mosquito vectors in Australia

T Hurst

School of Population Health, UQ Michael Brown, Brian Kay, Peter Ryan

Evaluation of Australian native fish and larvicides for the integrated control of freshwater mosquito vectors

C Monk

School of Medicine, UQ Lawrie Powell

Hereditary haemochromatosis: studies of its origins and its effects on quality of life

M Pearson

School of Population Health, UQ Don McManus, Alex Loukas

Identification, characterization and vaccine efficacy of membrane proteins of Schistosoma mansoni

C Pyke

Surgery, UQ Martin Lavin

Risk quantification, therapeutic morbidity and quality of life in breast cancer

A Pinzon-Charry

School of Population Health, UQ J Alejandro López

Characterisation of blood dendritic cells in patients with cancer

J Whitson

School of Population Health, UQ Denis Moss, Martin Lavin, Sharon Stils

Cellular transformation and expression profiling studies related to nasopharyngeal carcinoma

C Xu

Molecular and Cellular Pathology, UQ Peter Parsons

Evaluation of the efficacy and safety of sunscreens

Y Yang

School of Population Health, UQ Don McManus, Malcolm Jones

Epidemiological, clinical and molecular studies on Echinococcosis in Ningxia Hui automomous region, China

PhD

MPubHealth Scholars K Smith

School of Population Health, UQ David Whiteman

Risk factors for Barrett’s oesophagus

M Stickley

School of Population Health, UQ David Whiteman

Sun exposure and site specific melanoma

G Butler

School of Population Health, UQ David Whiteman

Non-steriodal anti-inflammatory drugs and skin cancer

M Shariff

Surgery, UQ Martin Lavin

Composition and enzymatic activities of ataxia-telangiectasia mutated (ATM) protein complexes

MPhil Scholars

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Queensland Institute of Medical Research

Student Name

University/Supervisors

Thesis Title

M Elliot

Southern Clinical Division, UQ Denis Moss, Joanne Davis

Immunological, virological and molecular biological analysis of nasopharyngeal carcinoma

A Rives

Integrative Biology, UQ Mark Breitfuss, Brian Kay

The toxic activity of Bacillus sphaericus in Culex annulirostris cadavers

M Chai

Microbiology and Parasitology, UQ Geoff Gobert, Don McManus

Ultrastructural investigation and gene expression profiling of the lung stage schistosomulum of Schistosoma japonicum

P Dickson

Biochemistry and Molecular Biology, UQ, Nick Martin

Fine mapping of the human ADH genes

J Hansen

Zoology and Entomology, UQ Nick Martin

Genetics of taste

A Marshall

School of Life Sciences, QUT Greg Anderson, Brian Harmon

The distribution and regulation of transferring receptor 1 in the small intestine

S Shekar

Zoology and Entomology, UQ Nick Martin

Genetics of wrinkling

P Sivadorai

Microbiology and Parasitology, UQ Malcolm Jones, Don McManus

The role of iron in embryogenesis of schistosomes

T Tran

Microbiology and Parasitology, UQ Sri Sriprakash

Evolution of Group G Streptococcal pathogenic variants

H Bofinger

School of Life Sciences, UQ Geoff Hill

Pegylated G-CSF promotes the augmentation of CD4 T cell regulatory function

J Challacombe

Health Sciences, UQ Peter Parsons

The role of granulocytes in the efficacy of PEP005 against skin tumours

L Major

School of Population Health, UQ Andreas Suhrbier, Grant Darnell

Bcl-xL and Bcl-2 bind the retinoblastoma tumour suppressor protein

R Moor

School of Life Sciences, QUT David Tscharke, Denis Moss

Assessing EBV specific CD8+ T cell function using CD 107 surface staining

M Neller

Science Faculty, QUT Chris Schmidt, Nathan Martinez

Ex vivo anti-tumour immunity directly correlates with clinical response to DC immunotherapy in Stage IV melanoma patients

C Perkins

Molecular and Microbial Sciences, UQ Alex Loukas

Molecular determinants of host range in blood-feeding parasites

N Richmond

School of Life Sciences, QUT Adèle Green

A molecular epidemiological analysis of divergent pathways to melanoma development

K Wynn

School of Life Sciences, QUT Rajiv Khanna

BARF1 and Epstein-Barr virus

K Broad

Biomolecular and Biomedical Science, GU Tom Sculley

Characterisation of the interaction of the Epstein-Barr virus nuclear antigen 6 with intracellular proteins

C Chang

Molecular and Microbial Sciences, UQ Alex Loukas

Masking immune recognition by Schistosomiasis mansoni

J Chia

Molecular and Microbial Sciences, UQ James McCarthy

The Immunogenic proteins of Pediculus humanus

L Nelson

Biotechnology, UQ James McCarthy

The role of sequence variation in HRPII in the performance of Rapid Diagnostic Test (RDTs) for malaria

MSc

BSc(Hons)

BApplSc(Hons)

BSc(Biotech)

Queensland Institute of Medical Research

71

Training and Education Program

Student Awards

Simon Apte

Basil Shaw Fellowship

Australian Rotary Health Research Fund, Brisbane, 2005

Wendy Chung

3rd Prize for Best Oral Presentation

School of Population Health Postgrad Conference, Brisbane, 2004

Amber Glanfield

Best Presentation for a Non-confirmed Student

School of Population Health Postgrad Conference, Brisbane, 2004

Tessa Knox

Oral Presentation Commendation

School of Population Health Postgrad Conference, Brisbane, 2004

Amber Glanfield

Best Student Poster Award

Australian Society for Parasitology Conference, Fremantle, 2004

Magda Ellis

Best Student Poster Award

Asia-Pacific Forum for Tropical Health, Cairns, 2004

Yang Yurong

Best Oral Communication by a Student

XXIst International Congress of Hydatidology, Kenya, 2004

Jason Jeffery

Outstanding Student Presentation

The Elizabeth N Marks Award, 2004

Jason Jeffery

Best Oral Presentation

School of Population Health Postgrad Conference, Brisbane, 2004

Tanya Russell

2nd Prize for Best Oral Presentation

School of Population Health Postgrad Conference, Brisbane, 2004

Leisl Packer

Student Excellence Award

Ausbiotech QLD Student Presentation and Questioning, 2004

Leisl Packer

Young Australian of the Year

Australian Government, 2005

Leisl Packer

Young Researcher Award

Cure Cancer Foundation of Australia Awards, 2005

Amila Suraweena

First Prize, 2 Year Oral Presentation

Bi-annual School of Medicine Postgrad Conference, Brisbane, 2004

Stephen Earl

First Prize, 2nd Year Oral Presentation

Bi-annual School of Medicine Postgrad Conference, Brisbane, 2004

Kelly Landers

First Prize, 3rd Year Oral Presentation

Bi-annual School of Medicine Postgrad Conference, Brisbane, 2004

Nathan Gillespie

Hans Eysenck Award for Genetics of Personality

2005

Michelle Neller

Best Oral Presentation

ASMR Student Conference, Brisbane, 2005

Jacqui Fleming

IM and MJ Mackerras Prize

nd

James Vincent Duhig Prize

Top marks in B App Sci (Medical Science)

JR Saal Prize Aust Ass of Clinical Biochemist Prize Albert Pinzon-Charry

72

Oral Presentation Award

ASMR Student Conference, Brisbane, 2005

Queensland Institute of Medical Research

Education Program

This year, involvement with students at all stages of their career has increased markedly with the number of higher degree research students enrolled at the Institute doubling since 2001.

Senior High School Students Forty-two schools attended the annual High School Lecture Series held at the end of July 2004. Schools participating included both state and private high schools from the CBD, Toowoomba, Sunshine and Gold Coast. The possibility of videoconferencing the lecture series to regional schools around Queensland is being investigated.

The Education Program received the Queensland Education Smart State 2004 Peter Doherty Award for Excellence in Science and Science Education by an Industry/ Business/ Research Institution in August 2004. The Award was based on a joint application which encompassed QIMR’s education and Indigenous student-teacher programs.

All Hallows, Hillbrook Anglican School, Moreton Bay College, Kelvin Grove SHS, Capalaba, and the Christian College Outreach Centre, Mansfield. Past students of Moreton Bay College, Dr Vicki Whitehall and Hillbrook Anglican School, Dr Danielle Stanisic visited their old schools to present and interact with students and share their experiences of a career in science. Education Officer, Simone Cross, was invited speaker at both the Coopers Plains Science Teachers Conference at Nyandra SHS and the Northside Teachers Conference at Northpoint TAFE. Eighty students from the UQ Biofutures program were toured through research laboratories and the Q-Gen cGMP facility.

talented students, including one Indigenous student worked at QIMR for 6 weeks over the summer vacation, and five of these elected to continue on at QIMR for their Honours degree.

Undergraduate Students Science students in their second or third university year can apply for QIMR competitive Summer Vacation Studentships which allow them to work on their own research project, with day-to-day supervision from staff members. Ten academically

Leisl Packer, PhD student in the Human Genetics lab, was named Young Queenslander of the Year. She emphasised that medical research is a team effort and shared her passion for science aimed at curing and preventing skin cancer with senior secondary school students outside and inside QIMR. Schools visited by QIMR during the 2004-2005 year included: Queensland Institute of Medical Research

High school students attending the High School Lecture Series held annually at QIMR

73

Awards

QIMR Bancroft Medallists

Derrick-Mackerras Memorial Lectures

Each year, an eminent member of the scientific community is chosen to deliver the Derrick-Mackerras Memorial Lecture, named for the founding Director and the founding Deputy Director of QIMR. The name Bancroft is synonymous with excellence in scientific and medical endeavour, and is an enduring memorial to the family whose efforts did so much to shape the direction of biomedical scholarship in the state of Queensland. The QIMR Bancroft Medal is awarded to those who have made an outstanding contribution to QIMR.

21st

2004 Dr James Watson

B2B – From Bone to B Cells

20th

2003 Professor Bob Williamson

Human Genes and Cloning People: The Medical Realities and the Public Fears

19th

2002 Professor Fiona Stanley

Public Health, Human Rights and the Development of Civil Societies. What has health and medical research got to do with social justice?

18th

2001 Sir Gustav Nossal

The Genomics Revolution to Prove a New Model for Spaceship Earth

17th

2000 John M Vierling MD

Human Organ Transplantation in the New Millennium: Understanding and Controlling the Immune Response

Ms Sue Cassidy (2004)

16th

1999 Professor Frank Fenner

Professor Peter Parsons (2003)

Disease Eradication and Bioterrorism: Opposite Ends of a Public Health Spectrum

15th

1998 Dr Lois “Lowitja” O’Donoghue

Indigenous Health: Monitoring the Vital Signs

14th

1997 Professor Peter Doherty

Killer Cells and the Control of Viral Infections

13th

1996 Professor Bridget M Ogilvie

The Support of Medical Research: People, Programs and Policies

12th

1995 Professor C Thomas Caskey

Genetics and the Future

11th

1994 Dr Baruch Blumberg

Evolution, Sex and the Hepatitis B Virus

10th

1993 Professor M FergusonSmith

Modern Genetics Research and its Consequences for Society

9th

1992 Professor J J Owen

Life and Death of Cells in the Immune System: Implications for Susceptibility to Infections and Disorders of the Immune Response

Professor Brian Kay (2000)

8th

1991 Professor Chev Kidson

Queensland Medical Laboratories (1999)

Genes, Galaxies and Ghosts! Science, Medicine and the Future of Man

7th

1989 Paul Ehrlich

Ecology and the Human Future: cosystems, Health and Public Health

Sullivan & Nicolaides (1999)

6th

1988 The Honourable Mike Ahern

Overview of the History of the Struggles and the Successes in the Development of Science and Technology Policy in Queensland

5th

1985 Dr Louis H Miller

Parasites and Mankind: The Challenge of Malaria in Human History

4th

1984 Dr Steven Jay Gould

Evolution Beyond Darwin

3rd

1983 Dr Robyn Williams

The Future of Medicine - Five Nightmares

2nd

1982 Dr Carleton Gajdusek

Unravelling Causes of Human Disease: Lessons From Adventures in East Asia and the Western Pacific

1st

1981 Professor Ralph Doherty

Major Contributions by Australians to Medical Science

Dr Suzanne Elliott (2003) Mrs Beth Dawe (2003) Mrs Verion Conley (2003) Ms Christine Borthwick (2002) Dr Peter Upcroft (2002) Mrs Heather Matthews (2001) Mr Erin Fleay (2001) Mr Chris Ward (2000) Mr Allan Stockman (2000)

Ms Michelle Lagana (1997) Ms Lee Casey (1996) Professor John Kerr Mr Fergus Wilson Mr Ted Cole Dr Ian Taylor Sir Bruce Watson Mr Rod Wylie OBE 74

Queensland Institute of Medical Research

QIMR Fellows

At the same event each year, outstanding individuals are named as Fellows of the Institute.

2004 Peter Wills 2003 Bryan Campbell Clive Berghofer Sam Coco 2002 Diana Cavaye Sr Regis Mary Dunne 2001 Phillip Desbrow William O’Sullivan 2000 Lawrie Powell Tom Veivers 1999 Michael Barry Kay Ellem Ian Taylor 1998 Michael O’Rourke 1997 Peter Doherty Paul Korner Stephen Lynch No awards 1996 1995 Ted Brown 1994 Mervyn Eadie Bryan Emmerson Ian Wilkey 1993 Graham Mitchell 1992 Michael Alpers Rod Wylie

Queensland Institute of Medical Research

1991 Chev Kidson Chamlong Harinasuta Peter Livingstone No awards 1990 1989 Sir Edward Stewart Tao Yixun 1988 Mike Ahern Neville McCarthy Sir Gustav Nossal Des O’Callaghan (posth) Frank Schofield No awards 1987 1986 Natth Bhamarapravati Louis Miller Sir Eric Saint Robert Shope Sir Bruce Watson 1985 Neville Davis Robert Porter Brian Wilson No awards 1984 1983 Sir Anthony Epstein Douglas Gordon Elizabeth Marks 1982 Carleton Gajdusek David Henderson Owen Powell Julie Sulianti Saroso Edwin Westaway Vincent Zigas

1981 Sir Macfarlane Burnet Ralph Doherty Frank Fenner Eric French Sir Abraham Fryberg Douglas Lee Margaret Macgregor Aubrey Pye William Reeves John Sprent Harry Standfast George Taylor John Tonge

75

Awards

Other Awards

Edward Morris Geoff Hill Kathy Andrews

Kathy Andrews

Stuart Olver Michael Good Brian Kay Daniel Wallace Dr Geoff Hill receives his 2005 Queenslander of the Year Award. Newspix/Hill/Quest Geoff

Amanda Spurdle

David Whiteman David Whiteman

Nick Martin

Richard Ruddell Daniel Wallace receiving the Queensland Premier’s Award for Best Abstract and Presentation at the ASMR Conference 2005

David Frazer Sandro Prato Greg Lawrence Ihor Misko

76

President’s Prize for Best Original Research Queenslander of the Year 2005 Queensland Premier’s Award for Medical Research finalist Best Poster Prize

Transplantation Society of Australia and NZ, 2004 Queensland State Government, 2005 Queensland State Government, 2005

Queensland Health and Medical Scientific Meeting, 2005 Best Poster Prize CRC-VT Annual Conference, Byron, 2005 Rubbo Medallion Rubbo Oration, ASM Sydney, 2004 Member of the Order of Queen’s Birthday Honours Australia (AM) List, 2005 Queensland Premier’s Queensland State Award and Medal for Government, 2005 Medical Research in Senior Postdoctoral Category Honorary QIMR 3rd Scientific Commendation for Conference, Noosa, 2004 Poster Prize Best Scientific QIMR 3rd Scientific Presentation Conference, Noosa, 2004 Best Scientific Paper Clive Berghofer Prize, QIMR, 2004 published by QIMR faculty Leadership and Ralph Doherty Award, 2004 Excellence in Medical Research June W Halliday Young Gastroenterological Society of Investigator Award Australia, 2004 Bushell Foundation Gastroenterological Society of Research Fellowship Australia, 2004 Best Poster Presentation BIG Meeting 2004 Long Service Award Over 25 years service to QIMR Long Service Award Over 25 years service to QIMR Queensland Institute of Medical Research

Grants and Funding

NHMRC Grants Awarded (Excluding Equipment Grants, Fellowships and Scholarships) Calendar Year:

2000

2001

2002

2003

2004

2005

148,383

717,557

900,623

2,745,278

3,574,000

4,793,386

Project Grants - Genomics

-

863,000

853,000

394,000

-

-

Program Grants

-

-

2,110,000

2,965,000

4,421,083

5,426,606

Transitional Institute Grant (TIG)

-

-

900,000

900,000

900,000

900,000

4,818,225

4,863,644

4,049,556

2,466,426

511,146

-

Development Grants

-

-

-

155,000

155,000

156,500

International Collaborative Grants

-

-

-

150,000

415,942

265,942

4,966,608

6,444,201

8,813,179

9,775,704

2000

2001

2002

2003

2004

2005

84,426

101,824

82,243

92,067

58,977

172,339

226,617

327,377

399,910

620,202

434,866

565,746

-

-

160,000

511,000

606,750

884,000

Research Fellowships

275,428

354,576

660,000

787,750

1,305,000

1,548,750

Total

586,471

783,777

1,302,153

2,011,019

2,405,593

3,170,835

2000

2001

2002

2003

2004

2005

249,649

212,812

432,773

381,265

312,818

280,568

Project Grants - Standard

Transitional Block Grant (TBG)

Total

9,977,171 11,542,434

NHMRC Fellowships and Scholarships Awarded Calendar Year: Postgraduate Scholarships Training Fellowships Career Development Awards

Leukaemia Foundation of Queensland Funding Calendar Year:

Leukaemia Foundation QLD

Queensland Institute of Medical Research

77

Grants and Funding

Major New Grants Awarded in 2004–2005 (over $100,000)

Source

Chief Investigators & Project Title

Term

Period

Total Funds or QIMR Component of Funds

ARC

HAYWARD N, KAY G : “The function of menin in mammalian development.” (Administered by The University of Queensland)

3 yrs

2005-07

$230,000

ARC

KHANNA K, FABBRO M : “Functional characterisation of CMAP, a novel centrosome and midbody-associated protein.” (Administered by Griffith University)

3 yrs

2005-07

$230,000

ARC

LAVIN M (UQ) et al. : “Venomics: molecular and functional analysis of Australian snake venoms for development of human therapeutics.”

(Administered by The University of Queensland)

3 yrs

2004-06

$521,325

CCNSW and QCF

BUTOW P et al. : “Quality of life and psychosocial predictors of outcome in a population based study of ovarian cancer.” (Multi-State Grant administered by University of Sydney; QLD PI: P WEBB)

2 yrs

2005-06

141,756

KOMEN

KHANNA K : “Characterisation of a novel protein implicated in breast cancer progression.”

3 yrs

2005-08

US$248,250

NBCF

CHENEVIX-TRENCH G : “Expression profiling of familial breast tumours.”

3 yrs

2005-07

$219,840

NHF

GOOD M : “Investigation of memory B-cells and long-lived plasma cells during group A streptococcal infection of mice immunised with candidate vaccines to prevent rheumatic fever and rheumatic heart disease : implications for vaccine design and administration.”

2 yrs

2005-06

$120,000

NHF

OLIVE C : “The development of a lipid core peptide-based vaccine against multiple virulence factors of group A streptococci to prevent rheumatic heart disease.”

2 yrs

2005-06

$120,000

NHMRC

BOYD A (UQ), BARTLETT P, TURNLEY A, GALEA M : “Is EphA4 the major molecular regulator of axonal regeneration?” (Administered by The University of Queensland)

3 yrs

2005-07

$227,250

NHMRC

DEVEREUX L : “Australian Biospecimen Network - Oncology.”

(Administered by Peter MacCallum Cancer Centre; QIMR Investigators: C SCHMIDT, G CHENEVIX-TRENCH)

5 yrs

2004-09

$234,300

NHMRC

FRAZER I, THOMAS R, HILL G : “Immunological therapies for cancer and autoimmunity.” (Administered by The University of Queensland; QIMR Investigator: G HILL)

5 yrs

2005-09

$1,355,000

NHMRC

KAY G, HAYWARD N : “Transcriptional targets of the MEN1 tumour suppressor in endocrine cancer.”

3 yrs

2005-07

$447,750

NHMRC

KELSO A, BAZ A : “Generation of multipotential memory CD8+ T cells.”

3 yrs

2005-07

$473,500

NHMRC

LAVIN M (UQ), GUEVEN N : “Functional role of aprataxin: mutated in ataxia with oculomotor apraxia.”

3 yrs

2005-07

$272,250

NHMRC

LAVIN M (UQ), SCOTT S : “Functional significance of ATM-dependent phosphorylation of Mre11.”

3 yrs

2005-07

$208,500

NHMRC

MARTIN N : “Mapping genes for anxiety and depression.”

3 yrs

2005-07

$751,200

NHMRC

MONTGOMERY G et al. : “Fine mapping of a significant linkage region 3 yrs for endometriosis.”

2005-07

$512,663

78

Queensland Institute of Medical Research

Source

Chief Investigators & Project Title

Term

Period

Total Funds or QIMR Component of Funds

NHMRC

MOWRY B et al. : “A genome-wide linkage study of schizophrenia in a large sample from Tamil Nadu, India.”

3 yrs

2005.07

$500,000

NHMRC

POWELL L, ANDERSON G, RAMM G, SUBRAMANIAM N : “Iron metabolism and liver disease.”

2005-09

$3,089,760

NHMRC

SPURDLE A et al. : “Molecular epidemiology of endometrial cancer.”

3 yrs

2005-07

$1,451,998

NIH

GOOD M et al. : “Global GAS vaccine based on the M-protein.”

5 yrs

2004-09

US$2,705,945

NIH

HEATH A : “MARC: Genetic epidemiology of alcoholism and comorbidity.” (Administered by Washington University in St Louis; QIMR Investigator: N MARTIN)

5 yrs

2004-09

US$500,000

QCF

GANDHI M et al. : “EBV-specific cytotoxic T lymphocytes as tools for adoptive immunotherapy for EBV-positive Hodgkin’s lymphoma.”

2 yrs

2005-06

$143,400

QCF

HAYWARD N : “Identification of novel tumour suppressor genes in melanoma using array-CGH.”

2 yrs

2005-06

$143,400

QCF

HILL G : “Host B cells and graft-versus-host disease.”

2 yrs

2005-06

$143,400

QCF

KHANNA K, CUMMINGS M, FURNIVAL C : “Characterisation of a novel protein involved in breast cancer progression.”

2 yrs

2005-06

$143,400

QCF

KIENZLE N, KELSO A : “In vivo functions od CD8 low T cells.”

2 yrs

2005-06

$143,400

QCF

LOFFLER K, HAYWARD N : “Molecular mechanisms of insulinoma development.”

2 yrs

2005-06

$143,400

QCF

SPRING K, LEGGETT B, YOUNG J : “Role of oncogenic BRAF (V599E) mutation in the molecular pathogenesis of sporadic colorectal cancer.”

2 yrs

2005-06

$143,400

QCF

YOUNG J, JASS J : “Characterisation of a novel syndrome of familial colorectal cancer based on the serrated pathway of tumour development.”

2 yrs

2005-06

$143,400

Legend for Source of Funds ARC

Australian Research Council

CCNSW

Cancer Council of New South Wales

KOMEN

Susan G Komen Breast Cancer Foundation (USA)

NBCF

National Breast Cancer Foundation

NHF

National Heart Foundation of Australia

NHMRC

National Health and Medical Research Council

NIH

National Institutes of Health (USA)

QCF

Queensland Cancer Fund

Queensland Institute of Medical Research

GRANTS FUNDING RECEIVED FROM ALL SOURCES 2004–2005 OTHER

QLD HEALTH QIMR TRUST

NIH NHMRC

79

2004–2005 Publications

Ahlbom A, Green A, Kheifets L, Savitz D and Swerdlow A; CNIRP Standing Committee on epidemiology. Epidemiology of heath effects of radiofrequency exposure. Environ Health Perspect 112: 1741-54, Review, 2004 Allen JD, Zhang XD, Scott CL, Boyle GM, Hersey P and Strasser A. Is Apaf-1 expression frequently abrogated in melanoma? Cell Death Differ 12: 680-1, 2005 Apte MV, Park S, Phillips PA, Santucci N, Goldstein D, Kumar RK, Ramm GA, Buchler M, Friess H, McCarroll JA, Keogh G, Merrett N, Pirola R and Wilson JS. Desmoplastic reaction in pancreatic cancer: role of pancreatic stellate cells. Pancreas 29: 179-87, 2004 Arnold JM, Huggard PR, Cummings M, Ramm GA and Chenevix-Trench G. Reduced expression of chemokine (C-C motif) ligand2(CCL2) in ovarian adenocarcinoma. Br J Cancer 92: 2024-31, 2005 Asojo OA, Goud G, Dhar K, Loukas A, Zhan B, Deumic V, Liu S, Borgstahl GE and Hotez PJ. X-ray structure of Na-ASP-2, a Pathogenesis-related-1 protein from the nematode parasite, Necator americanus, and a vaccine antigen for human hookworm infection. J Mol Biol 346: 801-14, 2005 Barton PS, Aberton JG, Bate I and Kay BH. Water levels and mosquito abundance at the Gippsland Lakes in eastern Victoria. Arbovirus Res Aust 9: 17-22, 2005 Bates TC, Castles A, Coltheart M, Gillespie N, Wright M and Martin NG. Behaviour genetic analyses of reading and spelling: a component processes approach. Aus J Psychol 56: 115-26, 2004 Beadle GF, Yates PM, Najman JM, Clavarino A, Thomson D, Williams G, Kenny L, Roberts S, Mason B and Schlect D. Beliefs and practices of patients with advanced cancer: implications for communication. Br J Cancer 91: 254-7, 2004 Berchuck A, Schildkraut JM, Wenham RM, Calingaert B, Ali S, Henriott A, Halabi S, Rodriguez GC, Gertig D, Purdie DM, Kelemen L, Spurdle AB, Marks J and Chenevix-Trench G. Progesterone receptor promoter +331A polymorphism is associated with a reduced risk of endometrioid and clear cell ovarian cancers. Cancer Epidemiol Biomarkers Prev 13: 2141-7, 2004 Binks MJ, Fernie-King BA, Seilly DJ, Lachmann PJ and Sriprakash KS. Attribution of the various inhibitory actions of the Streptococcal inhibitor of complement (SIC) to regions within the molecule. J Biol Chem 280: 20120-5, 2005

80

Birrell GW, Kneebone K, Nefedov M, Nefedova E, Jartsev MN, Mitsui M, Gatti RA and Lavin MF. ATM mutations, haplotype analysis, and immunological status of Russian patients with ataxia telangiectasia. Hum Mutat 25: 593, 2005

Chen N, Wilson DW, Pasay C, Bell D, Martin LB, Kyle D and Cheng Q. Origin and dissemination of chloroquine-resistant Plasmodium falciparum with mutant pfcrt alleles in the Philippines. Antimicrob Agents Chemother 49: 2102-5, 2005

Borg NA, Ely LK, Beddoe T, Macdonald WA, Reid HH, Clements CS, Purcell AW, KjerNielsen L, Miles JJ, Burrows SR, McCluskey J and Rossjohn J. The CDR3 regions of an immunodominant T cell receptor dictate the ‘energetic landscape’ of peptide-MHC recognition. Nat Immunol 6: 171-80, 2005

Chenevix-Trench G, Sinilnikova OM, Suthers G, Pandeya N, Mazoyer S, Sambrook JF, Goldup S, Goldgar D, Lynch HT, Lenoir GM and Cheetham G; kConFab. Ratio of male to female births in the offspring of BRCA1 and BRCA2 carriers. Famil Cancer 4: 73-5, 2005

Boutlis CS, Weinberg JB, Baker J, Bockarie MJ, Mgone CS, Cheng Q and Anstey NM. Nitric oxide production and nitric oxide synthase activity in malaria-exposed Papua New Guinean children and adults show longitudinal stability and no association with parasitemia. Infect Immun 72: 6932-8, 2004 Boyle GM, Martyn AC and Parsons PG. Histone deacetylase inhibitors and malignant melanoma. Pigment Cell Res 18: 160-6, 2005 Breitfuss MT, Hurst T, Ryan P and Kay B. Practical freshwater mosquito control: defining productive habitats and implementing effective control strategies. Arbovirus Res Aust 9: 52-7, 2005 Buscemi G, Perego P, Carenini N, Nakanishi M, Chessa L, Chen J, Khanna K and Delia D. Activation of ATM and Chk2 kinases in relation to the amount of DNA strand breaks.

Oncogene 23: 7691-700, 2004 Cardinal JW, Bergman L, Hayward N, Sweet A, Warner J, Marks L, Learoyd D, Dwight T, Robinson B, Epstein M, Smith M, Teh BT, Cameron DP and Prins JB. A report of a national mutation testing service for the MEN1 gene: clinical presentations and implications for mutation testing. J Med Genet 42: 69-74, 2005 Casey G, Lindor NM, Papadopoulos N, Thibodeau SN, Moskow J, Steelman S, Buzin CH, Sommer SS, Collins CE, Butz M, Aronson M, Gallinger S, Barker MA, Young JP, Jass JR, Hopper JL, Diep A, Bapat B, Salem M, Seminara D and Haile R; Colon Cancer Family Registry. Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer. JAMA 293: 799-809, 2005 Chang JH, Gertig DM, Chen X, Dite GS, Jenkins MA, Milne RL, Southey MC, McCredie MR, Giles GG, Chenevix-Trench G, Hopper JL and Spurdle AB. CYP17 genetic polymorphism, breast cancer, and breast cancer risk factors: Australian Breast Cancer Family Study. Breast Cancer Res 7: R513-21, 2005

Chhatwal GS and McMillan DJ. Uncovering the mysteries of invasive streptococcal diseases. Trends Mol Med 11: 152-5, 2005 Chin D, Boyle GM, Kane AJ, Theile DR, Hayward NK, Parson PG and Coman WB. Invasion and metastasis markers in cancers. Br J Plast Surg 58: 466-74, 2005 Chin D, Boyle GM, Williams RM, Ferguson K, Pandeya N, Pedley J, Campbell CM, Theile DR, Parsons PG and Coman WB. Novel markers for poor prognosis in head and neck cancer. Int J Cancer 113: 789-97, 2005 Chin D, Boyle GM, Williams RM, Ferguson K, Pandeya N, Pedley J, Campbell CM, Theile DR, Parsons PG and Coman WB. Alpha BCrystallin, a new independent marker for poor prognosis in head and neck cancer.

Laryngoscope 115: 1239-42, 2005 Clavarino AM, Janda M, Hughes KL, Del Mar C, Tong S, Stanton WR, Aitken JF, Leggett BA and Newman B. The view from two sides: a qualitative study of community and medical perspectives on screening for colorectal cancer using FOBT. Prev Med 39: 482-90, 2004 Colebrook AL, Jenkins DJ, Jones MK, Tatarczuch L and Lightowlers MW. Effects of cyclosporin A on the survival and ultrastructure of Echinococcus granulosus protoscoleces in vitro. Parasitology 129: 497504, 2004 Coventry WL and Keller MC. Estimating the extent of parameter bias in the classical twin design: a comparison of parameter estimates from the extended twin-family and classical twin designs. Twin Res Hum Genet 8: 214-23, 2005 Coventry WL, Gillespie NA, Heath AC and Martin NG. Perceived social support in a large community twin sample- age and sex differences. Soc Psychiatry Psychiatr Epidemiol 39: 625-36, 2004 Crough T, Burrows JM, Fazou C, Walker S, Davenport MP and Khanna R. Contemporaneous fluctuations in T cell responses to persistent herpes virus infections.

Eur J Immunol 35: 139-49, 2005

Queensland Institute of Medical Research

Crough T, Nieda M and Nicol AJ. Granulocyte colony-stimulating factor modulates alphagalactosylceramide responsive human Valpha24+Vbeta11+ NKT Cells. J Immunol 173: 4960-6, 2004

Elkington R and Khanna R. Cross-recognition of human alloantigen by cytomeglaovirus glycoprotein-specific CD4+ cytotoxic T lymphocytes: Implications for graft-versus-host diseases. Blood 105: 1362-4, 2005

Evans DM, Zhu G, Duffy DL, Montgomery GW, Frazer H and Martin NG. Major quantitative trait locus for eosinophil count is located on chromosome 2q. J Allergy Clin Immunol 114: 826-30, 2004

Crough T, Purdie DM, Okai M, Maksoud A, Nieda M and Nicol AJ. Modulation of human Valpha24(+)Vbeta11(+) NKT cells by age, malignancy and conventional anticancer therapies. Br J Cancer 91: 1880-6, 2004

Elkington R, Shoukry NH, Walker S, Crough T, Fazou C, Kaur A, Walker CM and Khanna, R. Cross-reactive recognition of human and primate cytomegalovirus sequences by human CD4 cytotoxi ymphocytes specific for glycoprotein B and H. Eur J Immunol 34: 3216-26, 2004

Evans DM, Zhu G, Duffy DL, Montgomery GW, Frazer IH, and Martin NG. Multivariate QTL linkage analysis suggests a QTL for platelet count on chromosome 19q. Eur J Hum Genet 12: 835-42, 2004

Currie BJ and McCarthy JS. Strongyloides stercoralis infection as a manifestation of immune restoration syndrome? Clin Infect Dis 40: 635, 2005 Darnell GA, Antalis TM, Rose BR and Suhrbier A. Silencing of integrated human papillomavirus type 18 oncogene transcription in cells expressing SerpinB2. J Virol 79: 424656, 2005 Dawood K, Kirk KM, Bailey JM, Andrews PW and Martin NG. Genetic and environmental influences on the frequency of orgasm in women. Twin Res Hum Genet 8: 27-33, 2005 Delatycki MB, Powell LW and Allen KJ. Hereditary hemochromatosis genetic testing of at-risk children: what is the appropriate age?

Genet Test 8: 98-103, Review, 2004 Dey N, McMillan DJ, Yarwood PJ, Joshi RM, Kumar R, Good MF, Sriprakash KS and Vohra H. High diversity group A Streptococcal emm types in an Indian community: the need to tailor multivalent vaccines. Clin Infect Dis 40: 46-51, 2005 Dietz HP, Hansell NK, Grace ME, Eldridge AM, Clarke B and Martin NG. Bladder neck mobility is a heritable trait. Br J Obstet Gynaecol 112: 334-9, 2005 Don TA, Jones MK, Smyth D, O’Donoghue P, Hotez P and Loukas A. A pore-forming hemolysin from the hookworm, Ancylostoma caninum. Int J Parasitol 34: 1029-35, 2004 Down M, Power M, Smith SI, Ralston K, Spanevello M, Burns GF and Boyd AW. Cloning and expression of the large zebrafish protocadherin gene, Fat. Gene Expr Patterns 5: 483-90, 2005 Edwards ML, Fagan PK, Currie BJ and Sriprakash KS. The fibronectin-binding capacity and host cell adherence of Streptococcus pyogenes strains are discordant with each other. Microbes Infect 6: 1156-62, 2004 Edwards ML, Fagan PK, Towers RJ, Currie BJ and Sriprakash KS. Inhibition of Streptococcus pyogenes adherence to HaCaT cells by a peptide corresponding to the streptococcal fibronectin-binding protein, Sfb 1, is strain dependent. Microbes Infect 6: 926-8, 2004

Queensland Institute of Medical Research

Elliott SR, Kuns RD and Good MF. Heterologous immunity in the absence of variant-specific antibodies after exposure to sub patent infection with blood-stage malaria.

Infect Immun 73: 2478-85, 2005 Ely LK, Green KJ, Beddoe T, Clements CS, Miles JJ, Bottomley SP, Zernich D, KjerNielsen L, Purcell AW, McCluskey J, Rossjohn J and Burrows SR. Antagonism of antiviral and allogeneic activity of a human public CTL clonotype by a single altered peptide ligand: implications for allograft rejection. J Immunol 174: 5593-601, 2005 Endo-Munoz L, Warby T, Harrich D and McMillan NA. Phosphorylation of HIV Tat by PKR increases interaction with TAR RNA and enhances transcription. Virol J 2: 17-29, 2005 Engwerda CR and Good MF. Interactions between malaria parasites and the host immune system. Curr Opin Immunol 17: 3817, 2005 Engwerda CR, Ato M and Kaye PM. Macrophages, pathology and parasite persistence in experimental visceral leishmaniasis. Trends Parasitol 20: 524-30, 2004 Engwerda CR, Ato M, Stager S, Alexander CE, Stanley AC and Kaye PM. Distinct roles for lymphotoxin-alpha and tumor necrosis factor in the control of Leishmania donovani infection. Am J Pathol 165: 2123-33, 2004 Engwerda CR, Beattie L and Amante FH. The importance of the spleen in malaria. Trends Parasitol 21: 75-80, Review, 2005 Evans DM, Kirk KM, Nyholt DR, Novac C and Martin NG. Teenage acne is influenced by genetic factors. Br J Dermatol 152: 579-81, 2005 Evans DM, Zhu G, Duffy DL, Frazer IH, Montgomery GW and Martin NG. A major quantitative trait locus for CD4-CD8 ratio is located on chromosome 11. Genes Immun 5: 548-52, 2004

Fabbro M, Savage K, Hobson K, Deans AJ, Powell SN, McArthur GA and Khanna KK. BRCA1-BARD1 complexes are required for p53Ser-15 phosphorylation and a G1/S arrest following ionizing radiation-induced DNA damage. J Biol Chem 279: 31251-8, 2004 Finnis M, Dayan S, Hobson L, ChenevixTrench G, Friend K, Ried K, Venter D, Woollatt E, Baker E and Richards RI. Common chromosomal fragile site FRA16D mutation in cancer cells. Hum Mol Genet 14: 1341-9, 2005 Frances SP, Cooper RD, Rowcliffe KL, Chen N and Cheng Q. Occurrence of Ross River virus and Barmah Forest virus in mosquitoes at Shoalwater Bay Military Training Area, Queensland, Australia. J Med Entomol 41: 115-20, 2004 Frazer DM, Inglis HR, Wilkins SJ, Millard KN, Steele TM, McLaren GD, McKie AT, Vulpe CD and Anderson GJ. Delayed hepcidin response explains the lag period in iron absorption following a stimulus to increase erythropoiesis. Gut 53: 1509-15, 2004 Frazer DM, Wilkins SJ, Millard KN, McKie AT, Vulpe CD and Anderson GJ. Increased hepcidin expression and hypoferraemia associated with an acute phase response are not affected by inactivation of HFE. Br J Haematol 126: 434-6, 2004 Gandhi M and Khanna R. Human Cytomegalovirus: Clinical aspects, immune regulation, and emerging treatments. Lancet Infect Dis 4: 725-38, Review, 2004 Gardiner DL, Dixon MW, Spielmann T, Skinner-Adams TS, Hawthorne PL, Ortega MR, Kemp DJ and Trenholme KR. Implication of a Plasmodium falciparum gene in the switch between asexual reproduction and gametocytogenesis. Mol Biochem Parasitol 140: 153-60, 2005 Gatton M, Kay B and Ryan P. Ross River virus outbreaks in south east Queensland: what notification data can tell us. Arbovirus Res Aust 9: 122-5, 2005 Gatton ML and Cheng Q. Modeling the development of acquired clinical immunity to Plasmodium falciparum malaria. Infect Immun 72: 6538-45, 2004

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2004–2005 Publications

Gatton ML and Cheng Q. Investigating antigenic variation and other parasite-host interactions in Plasmodium falciparum infections in naïve hosts. Parasitololgy 128: 367-76, 2004

Good MF, Stanisic D, Xu H, Elliott S and Wykes M. The immunological challenge to developing a vaccine to the blood stages of malaria parasites. Immunol Rev 201: 254-67, Review, 2004

Gatton ML and Cho-Min-Naing. Costs to the patient for seeking malaria care in Myanmar.

Acta Tropica 92: 173-7, 2004

Good MF, Xu H, Wykes M and Engwerda CR. Development and regulation of cell-mediated immune responses to the blood stages of malaria: implications for vaccine Research.

Annu Rev Immunol 23: 69-99, Review, 2005

Gatton ML, Kay BH and Ryan PA. Environmental predictors of Ross River virus disease outbreaks in Queensland, Australia.

Am J Trop Med Hyg 72: 792-9, 2005 Gatton, ML, Kelly-Hope LA, Kay BH and Ryan PA. Spatial-temporal analysis of Ross River virus disease patterns in Queensland, Australia. Am J Trop Med Hyg 71: 629-35, 2004 Gatton ML, Martin LB and Cheng Q. Evolution of resistance to sulfadoxinepyrimethamine in Plasmodium falciparum parasites. Antimicrob Agents Chemother 48: 2116-23, 2004 Geraghty CM and McCarthy JS. Japanese encephalitis vaccine: is it being sufficiently used in travellers? Med J Aust 181: 269-70, 2004

Good MF. Australians lead the way in vaccine research for malaria and other infectious diseases. Aust Life Scientist March/April Edition, p23, 2005 Good MF. Genetically modified Plasmodium highlights the potential of whole parasite vaccine strategies. Trends Immunol 26: 295-7, 2005 Good MF. Vaccine-induced immunity to malaria parasites and the need for novel strategies. Trends Parasitol 21: 29-34, Review, 2005 Good MF. Wise to the healthy, wealthy divide.

In Griffith Review 4, ABC Books. pp175-84, 2004

Gillespie NA, Evans DE, Wright MM and Martin NG. Genetic simplex modeling of Eysenck’s dimensions of personality in a sample of young Australian twins. Twin Res 7: 637-48, 2004

Goodarzi AA, Jonnalagadda JC, Douglas P, Young D, Ye R, Moorhead GB, Lees-Miller SP and Khanna KK. Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A. Embo J 23: 4451-61, 2004

Gillespie NA, Whitfield JB, Williams B, Heath AC and Martin NG. The relationship between stressful life events, the serotonin transporter (5-HTTLPR) genotype and major depression.

Psychol Med 35: 101-11, 2005

Graves N, McKinnon L, Leggett B and Newman B. Re-interpreting the data on the cost and effectiveness of population screening for colorectal cancer in Australia. Aust New Zealand Health Policy 2: 10, 2005

Gobert GN and McManus DP. Update on paramyosin in parasitic worms. Parasitol Int 54: 101-7, 2005

Green KJ, Miles JJ, Tellam J, van Zuylen WJ, Connolly G and Burrows SR. Potent T cell response to a class I-binding 13-mer viral epitope and the influence of HLA micropolymorphism in controlling epitope length. Eur J Immunol 34: 2510-9, 2004

Gomez Gallego S, Loukas A, Slade RW, Neva FA, Varatharajalu R, Nutman TB and Brindley PJ. Identification of an astacin-like metalloproteinase transcript from the infective larvae of Strongyloides stercoralis. Parasitol Int 54: 123-33, 2005 Gonzalez LM, Montero E, Morakote N, Puente S, Diaz De Tuesta JL, Serra T, LopezVelez R, McManus DP, Harrison LJ, Parkhouse RM and Garate T. Differential diagnosis of Taenia saginata and Taenia saginata asiatica taeniasis through PCR. Diagn Microbiol Infect Dis 49: 183-8, 2004 Good MF and Kemp DJ. Overview of vaccine strategies for malaria. In: New Generation Vaccines. Eds. Levine MM, Kaper JB, Rappuoli R, Liu MA and Good MF. Marcel Dekker Inc., NY. pp847-9, 2004

82

Greer RM, Buntain HM, Lewindon PJ, Wainwright CE, Potter JM, Wong JC, Francis PW, Batch JA and Bell SC. Vitamin A levels in patients with CF are influenced by the inflammatory response. J Cyst Fibros 3: 143-9, 2004 Gupta A, Sharma GG, Young CS, Agarwal M, Smith ER, Paull TT, Lucchesi JC, Khanna KK and Ludwig T and Pandita TK. Involvement of human MOF in ATM function. Mol Cell Biol 25: 5292-305, 2005 Hall WD, Morley KI and Lucke JC. The prediction of disease risk in genomic medicine. Embo Rep 5: S22-6, 2004

Handoko HY, Nyholt DR, Hayward NK, Nertney DA, Hannah DE, Windus LC, McCormack CM, Smith HJ, Filippich C, James MR and Mowry BJ. Separate and interacting effects within the catechol-Omethyltransferase (COMT) are associated with schizophrenia. Mol Psychiatry 10: 589-97, 2005 Hansell NK, Dietz HP, Treloar SA, Clarke B and Martin NG. Genetic covariation of pelvic organ and elbow mobility in twins and their sisters. Twin Res 7: 254-60, 2004 Hansell NK, Wright MJ, Geffen GM, Geffen LB and Martin NG. Genetic influence on cognitive processes associated with distraction: an event-related potential study of the slow wave. Aust J Psychol 56: 89-98, 2004 Heath DD, Zhang, LH and McManus DP. Short Report: Inadequacy of yaks as hosts for the sheep dog strain of Echinococcus granulosus or for E. multilocularis. Am J Trop Med Hyg 72: 289-90, 2005 Herrera S, Bonelo A, Perlaza BL, Valencia AZ, Cifuentes C, Hurtado S, Quintero G, López JA, Corradin G and Arevalo-Herrera M. Use of long synthetic peptides to study the antigenicity and immunogenicity of the Plasmodium vivax circumsporozoite protein.

Int J Parasitol 34: 1535-46, 2004 Hoekstra C, Meijer P, Kluft C, Heutink P, Smit G, de Geus E, Smit JH, van Bruggen A, Montgomery GW, and Boomsma DI. Genetics of dizygotic twinning: a feasibility study for a Biobank. Twin Res 7: 556-63, 2004 Holliday E, Mowry B, Chant D and Nyholt D. The importance of modelling heterogeneity in complex disease: application to NIMH Schizophrenia Genetics Initiative data. Hum Genet 117: 160-7, 2005 Horvath A, Olive C, Karpati L, Sun HK, Good M and Toth I. Toward the development of a synthetic group A streptococcal vaccine of high purity and broad protective coverage. J Med Chem 47: 4100-4, 2004 Hotez PJ, Brooker, S, Bethony, JM, Bottazzi ME, Loukas A and Xiao S. Hookworm infection. New Eng J Med 351: 799-807, Review, 2004 Hsieh GC, Loukas A, Bhatia M, Wahl AM, Wang Y, Williamson AL, Kehn KW, Maruyama H, Hotez PJ, Leitenberg D, Bethony J and Constant SL. A secreted protein from the human hookworm necator americanus binds selectively to NK cells and induces IFNgamma �production. J Immunol 173: 2699704, 2004

Queensland Institute of Medical Research

Hugo L, Eaglesham G, Holling N, Kay B and Ryan P. Mosquito age grading techniques: old versus new. Arbovirus Res Aust 9: 137-42, 2005 Hurst T, Ryan P, Brown M and Kay B. Fishing for a mosquito control agent. Arbovirus Res Aust 9: 143-7, 2005 Hurst TP, Brown MD and Kay BH. Laboratory evaluation of the predation efficacy of native Australian fish on Culex annulirostris (Diptera: Culicidae). J Am Mosq Control Assoc 20: 28691, 2004 Jackson DC, Lau YF, Le T, Suhrbier A, Deliyannis G, Cheers C, Smith C, Zeng W and Brown LE. A totally synthetic vaccine of generic structure that targets Toll-like receptor 2 on dendritic cells and promotes antibody or cytotoxic T cell responses. Proc Natl Acad Sci U S A 101: 15440-5, 2004

Jones MK, Gobert GN, Zhang L, Sunderland P and McManus DP. The cytoskeleton and motor proteins of human schistosomes and their roles in surface maintance and host-parasite interactions. Bioessays 26: 752-65, 2004 Jones MK, Randall LM, McManus DP and Engwerda CR. Laser microdissection microscopy in parasitology: microscopes meet thermocyclers. Trends Parasitol 20: 502-6, Review, 2004 Kambara T, Simms LA, Whitehall VL, Spring KJ, Wynter CV, Walsh MD, Barker MA, Arnold S, McGivern A, Matsubara N, Tanaka N, Higuchi T, Young J, Jass JR and Leggett BA. BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum. Gut 53: 1137-44, 2004 Kay B and Vu SN. New strategy against Aedes aegypti in Vietnam. Lancet 365: 613-7, 2005

Jakob B, Rudolph JH, Gueven N, Lavin MF and Taucher-Scholz G. Live cell imaging of heavy-ion induced radiation responses by beamline microscopy. Radiat Res 163: 68190, 2005

Kaye PM, Svensson M, Ato M, Maroof A, Polley R, Stager S, Zubairi S and Engwerda CR. The immunopathology of experimental visceral leishmaniasis. Immunol Rev 201: 239-53, Review, 2004

James MR, Hayward NK, Dumenil T, Montgomery GW, Martin NG and Duffy DL. Epidermal growth factor gene (EGF) polymorphism and risk of melanocytic neoplasia. J Invest Dermatol 123: 760-2, 2004

Kelemen L, James M, Spurdle A, Campbell I, Chang-Claude J, Peel D, Anton-Culver H, Berchuck A, Schildkraut J, Whittemore A, McGuire V, Dicioccio RA, Duffy D and Chenevix-Trench G. BRAF polymorphisms and the risk of ovarian cancer of low malignant potential. Gynecol Oncol 97: 80712, 2005

Jass JR, Whitehall VL, Young J and Leggett BA. DNA methylation in colorectal cancer.

In: DNA Methylation and Cancer Therapy. Ed. Moshe Szyf. Landes Bioscience. pp59-68, 2004 Jeffery J, Foley D, Kay B and Ryan P. Know thine enemy - biology of brackish-water vectors in Maroochy Shire, Queensland.

Arbovirus Res Aust 9: 153-8, 2005 Jekimovs CR, Chen X, Arnold J, Gatei M, Richard DJ, Spurdle AB, Khanna KK and Chenevix-Trench G; kConFab Investigators.

Low frequency of CHEK2 1100delC allele in Australian multiple-case breast cancer families: functional analysis in heterozygous individuals. Br J Cancer 92: 784-90, 2005 Johnson BJ, Le TT, Dobbin CA, Banovic T, Howard CB, Flores Fde M, Vanags D, Naylor DJ, Hill GR and Suhrbier A. Heat shock protein 10 inhibits lipopolysaccharideinduced inflammatory mediator production. J Biol Chem 280: 4037-47, 2005 Jones M K, Beveridge I, Campbell RA and Palm HW. Terminology of the sucker-like organs of the scolex of trypanorhynch cestodes. Syst Parasitol 59: 121-6, Review, 2004

Queensland Institute of Medical Research

Kelemen L, Spurdle AB, Purdie DM, Gertig D and Chenevix-Trench G. RAD52 Y415X truncation polymorphism and epithelial ovarian cancer risk in Australian women.

Cancer Lett 218: 191-7, 2005 Keller MC and Coventry WL. Quantifying and addressing parameter indeterminacy in the classical twin design. Twin Res Hum Genet 8: 201-13, 2005 Kelly-Hope LA, Prudie DM and Kay BH. Differences in climatic factors between Ross River virus disease outbreak and nonoutbreak years. J Med Entomol 41: 1116-22, 2004 Kelly-Hope LA, Purdie DM and Kay BH. El Nino Southern Oscillation and Ross River virus outbreaks in Australia. Vector Borne Zoonotic Dis 4: 210-3, 2004 Kennedy GA, Butler J, Western R, Morton J, Hill G and Durrant S. Predicting survival for myeloid leukaemia after HLA-identical sibling donor allogeneic stem cell transplantation.

Leukemia 19: 317-8, 2005

Khan N, Hislop A, Gudgeon N, Cobbold M, Khanna R, Nayak L, Rickinson AB and Moss PA. Herpesvirus-specific CD8 T cell immunity in old age: Cytomegalovirus impairs the response to a coresident EBV infection. J Immunol 173: 7481-9, 2004 Khanna KK and Chenevix-Trench G. ATM and genome maintenance: defining its role in breast cancer susceptibility. J Mammary Gland Biol Neoplasia. 9: 247-62, Review, 2004 Khanna R, Moss D and Gandhi M. Technology Insight: applications of emerging immunotherapeutic strategies for EpsteinBarr Virus-associated malignancies. Nat Clin Practice Oncol 2: 138-49, 2005 Khanna R. Protocols in Adoptive Immunotherapy: Book Review. Immunol Cell Biol 83: 313, 2005 Kienzle N, Baz A and Kelso A. Profiling the CD8low phenotype, an alternative career choice for CD8 T cells during primary differentiation. Immunol Cell Biol 82: 75-83, Review, 2004 Kienzle N, Olver S, Buttigieg K, Groves P, Janas ML, Baz A and Kelso A. Progressive differentiation and commitment of CD8+ T cells to a poorly cytolytic CD8low phenotype in the presence of IL-4. J Immunol 174: 20219, 2005 Knopik VS, Heath AC, Madden PA, Bucholz KK, Slutske WS, Nelson EC, Statham D, Whitfield JB and Martin NG. Genetic effects on alcohol dependence risk: re-evaluating the importance of psychiatric and other heritable risk factors. Psychol Med 34: 1519-30, 2004 Knox T, Nam VS, Yen NT, Kay B and Ryan P. Optimising surveillance for dengue vector immatures in large water storage containers in Vietnam. Arbovirus Res Aust 9: 184-7, 2005 Korsinczky M, Fisher K, Chen N, Baker J, Rieckmann K and Cheng Q. Sulfadoxine resistance in Plasmodium vivax is associated with a specific amino acid in dihydropteroate synthase at the putative sulfadoxine-binding site. Antimicrobial Agents Chemotherapy 48: 2214-22, 2004 Kotze AC, Clifford S, O’Grady J, Behnke JM and McCarthy JS. An in vitro larval motility assay to determine anthelmintic sensitivity for human hookworm and Stronglyloides species.

Am J Trop Med Hyg 71: 608-16, 2004 Kotze AC, Coleman GT, Mai A and McCarthy JS. Field evaluation of anthelmintic drug sensitivity using in vitro egg hatch and larval motility assays with Necator americanus recovered from human clinical isolates. Int J Parasitol 35: 445-53, 2005

83

2004–2005 Publications

Laha T, Loukas A, Smyth DJ, Copeland CS and Brindley PJ. The fugitive LTR retrotransposon from the genome of the human blood fluke, Schistosoma mansoni. Int J Parasitol 34: 1365-75, 2004

Lin H, Nieda M and Nicol AJ. Differential proliferative response of NKT cell subpopulations to in vitro stimulation in the presence of different cytokines. Eur J Immunol 34: 2664-71, 2004

Landers KA, Burger MJ, Tebay MA, Purdie DM, Scells B, Samaratunga H, Lavin MF and Gardiner RA. Use of multiple biomarkers for a molecular diagnosis of prostate cancer. Int J Cancer 114: 950-6, 2005

Linn ML, Eble JA, Lübken C, Slade RW, Heino J, Davies J and Suhrbier A. An arthritogenic alphavirus uses the alpha 1 beta 1 integrin collagen receptor. Virology 336: 229-39, 2005

Latunde-Dada GO, Vulpe CD, Anderson GJ, Simpson RJ and McKie AT. Tissuespecific changes in iron metabolism genes in mice following phenylhydrazine-induced haemolysis. Biochim Biophys Acta 1690: 16976, 2004. Erratum in: Biochim Biophys Acta 1740: 91, 2005 Lavin MF, Birrell G, Chen P, Kozlov S, Scott S and Gueven N. ATM signaling and genomic stability in response to DNA damage. Mutat Res 569: 123-32, Review, 2005 Lavin MF, Scott S, Gueven N, Kozlov S, Peng C and Chen P. Functional consequences of sequence alterations in the ATM gene. DNA Repair 3: 1197-205, Review, 2004 Lavin MF. The Mre11 complex and ATM: a two-way functional interaction in recognising and signalling DNA double strand breaks.

DNA Repair 3: 1515-20, Review, 2004.

Erratum in: DNA Repair(Amst) 4: 519, 2005 Le AT, Miller PW, Heath AC and Martin N. Early childhood behaviours, schooling and labour market outcomes: estimates from a sample of twins. Econ Edu Rev 24: 1-17, 2005 Le TH, McManus DP and Blair D. Codon usage and bias in mitochondrial genomes of parasitic platyhelminths. Korean J Parasitol 42: 159-67, 2004 Lea RA, Nyholt DR, Curtain RP, Ovcaric M, Sciascia R, Bellis C, Macmillan J, Quinlan S, Gibson RA, McCarthy LC, Riley JH, Smithies YJ, Kinrade S and Griffiths LR. A genome-wide scan provides evidence for loci influencing a severe heritable form of common migraine. Neurogenetics 6: 67-72, 2005 Lessov CN, Martin NG, Statham DJ, Todorov AA, Slutske WS, Bucholz KK, Heath AC and Madden PA. Defining nicotine dependence for genetic research: evidence from Australian twins. Psychol Med 34: 865-79, 2004 Li YS, Kardorff R, Richter J, Sun KY, Zhou H, McManus DP and Hatz C. Ultrasound organometry: the importance of body height adjusted normal ranges in assessing liver and spleen parameters among Chinese subjects with Schistosoma japonicum infection. Acta Trop 92: 133-8, 2004

84

Loehlin JC, Jönsson EG, Gustavsson JP, Schalling M, Medland SE, Montgomery GW, and Martin NG. Gender diagnosticity and androgen receptor gene CAG repeat sequence.

Twin Res 7: 456-61, 2004 Loh E, Peter F, Subramaniam VN and Hong W. Mammalian Bet3 functions as a cytosolic factor participating in transport from the ER to the Golgi apparatus. J Cell Sci 118: 1209-22, 2005 Loukas A, Constant SL and Bethony JM. Immunobiology of hookworm infection. FEMS Immunol Med Microbiol 43: 115-24, 2005 Luciano M, Leisser R, Wright MJ and Martin NG. Personality, arousal theory and the relationship to cognitive ability as measured by inspection time and IQ. Pers Individ Dif 37: 1081-9, 2004 Luciano M, Wright MJ, Geffen GM, Geffen LB, Smith GA and Martin NG. Multivariate genetic analysis of cognitive abilities in an adolescent twin sample. Aust J Psychol 56: 79-88, 2004 Lynskey MT, Glowinski AL, Todorov AA, Bucholz KK, Madden PA, Nelson EC, Statham DJ, Martin NG and Heath AC. Major depression disorder, suicidal ideation and suicide attempt in twins discordant for cannabis dependence and early-onset cannabis use. Arch Gen Psychiatry 61: 102632, 2004 Macdonald GA and Prins JB. Peroxisomal fatty acid metabolism, peroxisomal proliferatoractivated receptors and non-alcoholic fatty liver disease. J Gastroenterol Hepatol 19: 1335-7, Review, 2004 Macdonald KP, Rowe V, Clouston A, Welply JK, Kuns RD, Ferrara JL, Thomas R and Hill GR. Cytokine expanded myeloid precursors function as regulatory antigen-presenting cells and promote tolerance through IL-10producing regulatory T cells. J Immunol 174: 1841-50, 2005

Manton KJ, Douglas ML, Netzell-Arnett S, Fitzpatrick DR, Nicol DL, Boyd AW, Clements JA and Antalis TM. Hypermethylation of the 5’CpG island of the gene encoding the serine protease Testisin promotes its loss in testicular tumorigenesis. Br J Cancer 92: 760-9, 2005 McArthur J, Medina E, Mueller A, Chin J, Currie BJ, Sriprakash KS, Talay SR, Chhatwal GS and Walker MJ. Intranasal vaccination with streptococcal fibronectin binding protein Sfb1 fails to prevent growth and dissemination of Streptococcus pyogenes in a murine skin infection model. Infect Immun 72: 7342-5, 2004 McCarthy JS. Malaria chemoprophylaxis: in war and peace. Med J Aust 182: 148-9, 2005 McGivern A, Wynter CV, Whitehall VL, Kambara T, Spring KJ, Walsh MD, Barker MA, Arnold S, Simms LA, Leggett BA, Young J and Jass JR. Promoter hypermethylation frequency and BRAF mutations distinguish hereditary non-polyposis colon cancer from sporadic MSI-H colon cancer. Famil Cancer 3: 101-7, 2004 McManus DP, Feng Z, Guo J, Li Y, Bartley PB, Loukas A and Williams GM. Pathways to improved, sustainable morbidity control and prevention of schistosomiasis in the People’s Republic of China. In: Schistosomiasis. Series: Worl Class Parasites. Eds. Secor WE and Colley DG. Springer. V.10: pp.159-75, 2005 McManus DP. A vaccine for Asian schistosomiasis. Curr Trends Immunol 5: 8190, 2004 McManus DP. Echinococcus granulosus and E. multilocularis - molecular diagnosis. In: Encyclopedia of Diagnostic Genomics and Proteomics. Eds. Fuchs J and Podda M. Marcel Dekker. pp. 374-9, 2004 McManus DP. Molecular taxonomy and epidemiology of cystic echinococcosis. SE Asian J Trop Med Pub Hlth 35 Suppl 1: 200-5, 2004 McMillan DJ and Chhatwal GS. Prospects for a group A streptococcal vaccine. Curr Opin Mol Ther 7: 11-6, Review, 2005 McMillan DJ, Batzloff MR, Browning CL, Davies MR, Good MF, Sriprakash KS, Janulczyk R, and Rasmussen M. Identification and assessment of new vaccine candidates for group A streptococcal infections. Vaccine 22: 2783-90, 2004

Mansilla MA, Kimani J, Mitchell LE, Christensen K, Boomsma DI, Daack-Hirsch S, Nepomucena B, Wyszynski DF, Felix TM, Martin NG and Murray JC. Discordant MZ twins with cleft lip and palate: a model for identifying genes in complex traits. Twin Res Hum Genet 8: 39-46, 2005

Queensland Institute of Medical Research

McNaughton SA, Marks GC, Gaffney P, Williams G and Green A. Validation of a food- frequency questionnaire assessment of carotenoid and vitamin E intake using weighed food records and plasma biomarkers: the method of triads model. Eur J Clin Nutr 59: 211-8, 2005 McNaughton SA, Marks GC, Gaffney P, Williams G and Green AC. Antioxidants and basal cell carcinoma of the skin: A nested case-control study. Cancer Causes Control 16: 609-18, 2005 Miller P, Mulvey C and Martin NG. Birth weight and schooling and earnings: estimates from a sample of twins. Econ Lett 86: 387-92, 2005 Miller PW, Mulvey C and Martin N. A test of the sorting model of education in Australia.

Econ Edu Rev 23: 473-82, 2004 Milward EA, Trinder D, Wilcox CE, Britton RS, Ramm GA and Olynyk JK. Is HFE involved in increased hepcidin expression and hypoferremia in inflammation and anemia of chronic disease? Hepatology 41: 936-8, 2005 Mitchell GF and Good MF. Historical review: Sir Gustav Nossal – immunologist and more.

Trends Immunol 25: 665-9, 2004 Montgomery GW, Zhao ZZ, Marsh AJ, Mayne R, Treloar SA, James M, Martin NG, Boomsma DI, and Duffy DL. A deletion mutation in GDF9 in sisters with spontaneous DZ twins.

Twin Res 7: 548-55, 2004 Morales ME, Kalinna BH, Heyers O, Mann VH, Schulmeister A, Copeland CS, Loukas A and Brindley PJ. Genomic organization of the Schistosoma mansoni aspartic protease gene, a platyhelminth orthologue of mammalian lysosomal cathepsin D. Gene 338: 99-109, 2004 Mounsey KE, Holt DC, Fischer K, Kemp DJ, Currie BJ and Walton SF. Analysis of Sarcoptes scabiei finds no evidence of infection with Wolbachia. Int J Parasitol 35: 131-5, 2005 Murphy MF and Neale R. Harms and benefits of screening to prevent cervical cancer. Lancet 364: 1484-85, 2004 Mylonas AD, Harley D, Purdie DM, Pandeya N, Vecchio PC, Farmer JF and Suhrbier A. Steroid therapy in an alphaviral arthritis. JCR- J Clin Rheumatol 10: 326-30, 2004 Nagasaka T, Sasamoto H, Notohara K, Cullings HM, Takeda M, Kimura K, Kambara T, MacPhee DG, Young J, Leggett BA, Jass JR, Tanaka N and Matsubara N. Colorectal cancer with mutation in BRAF, KRAS and wild-type with respect to both oncogenes showing different patterns of DNA methylation. J Clin Oncol 22: 4584-94, 2004

Queensland Institute of Medical Research

Nam VS, Kay B, Yen NT, Ryan P and Bektas A. Community mobilization, behaviour change and biological control in the prevention and control of dengue fever in Viet Nam. Dengue Bull 28: 57-61, 2004

Powell LW, Dixon JL and Hewett DG. Role of early case detection by screening relatives of patients with HFE-associated hereditary haemochromatosis. Best Pract Res Clin Haematol 18: 221-34, 2005

Neale RE, Darlington S, Murphy MF, Silcocks PB, Purdie DM and Talback M. The effects of twins, parity and age at first birth on cancer risk in Swedish women. Twin Res Hum Genet 8: 156-62, 2005

Prato S, Maxwell T, Pinzón-Charry A, Schmidt CW, Corradin G, and López JA. MHC class I-restricted exogenous presentation of a synthetic 102-mer malaria vaccine polypeptide. Eur J Immunol 35: 681-9, 2005

Neale RE, Mineau G, Whiteman DC, Brownbill PA and Murphy MF. Childhood and adult cancer in twins: Evidence from the Utah genealogy. Cancer Epidemiol Biomarkers Prev 14: 1236-40, 2005

Ralston KJ, Hird SL, Zhang X, Scott JL, Jin B, Thorne RF, Berndt MC, Boyd AW and Burns GF. The LFA-1- associated molecule PTA-1(CD226) on T cells forms a dynamic molecular complex with protein 4.1G and human discs large. J Biol Chem 279: 3381628, 2004

Neale RE, Purdie DM, Murphy MF, Mineau GP, Bishop T and Whiteman DC. Twining and the incidence of breast and gynecological cancers (United States). Cancer Causes Control 15: 829-35, 2004 Olive C, Hsien K, Horvath A, Clair T, Yarwood P, Toth I and Good MF. Protection against group A streptococcal infection by vaccination with self-adjuvanting lipid core M protein peptides. Vaccine 23: 2298-303, 2005 Pandeya N, Purdie DM, Green A and Williams G. Repeated occurrences of basal cell carcinoma of the skin and multi-failure survival analysis: follow-up data from the Nambour Skin Cancer Prevention Trial. Am J Epidemiol 161: 748-54, 2005 Peng Y, Woods RG, Beamish H, Ye R, Lees-Miller SP, Lavin MF and Bedford JS. Deficiency in the catalytic subunit of DNAdependent protein kinase causes downregulation of ATM. Cancer Res 65: 1670-7, 2005 Pereira TN, Lewindon PJ, Smith JL, Murphy TL, Lincoln DJ, Shepherd RW and Ramm GA. Serum markers of hepatic fibrogenesis in cystic fibrosis liver disease. J Hepatol 41: 576-83, 2004 Perez O, Bracho G, Lastre M, Mora N, del Campo J, Gil D, Zayas C, Acevedo R, Gonzalez D, López JA, Taboada C, Turtle C and Solis RL. Novel adjuvant based on a proteoliposome-derived cochleate structure containing native lipopolysaccharide as a pathogen-associated molecular pattern.

Immunol Cell Biol 82: 603-10, 2004 Phelan CM, Dapic V, Tice B, Favis R, Kwan E, Barany F, Manoukian S, Radice P, van der Luijt RB, van Nesselrooif BP, ChenevixTrench G, kConFab, Caldes T, de la Hoya M, Lindquist S, Tavtigian SV, Goldgar D, Borg A, Narod SA and Monteiro AN. Classification of BRCA1 missense variants of unknown clinical significance. J Med Genet 42: 138-46, 2005

Ramachandran V, McArthur JD, Behm CE, Gutzeit C, Dowton M, Fagan PK, Towers R, Currie B, Sriprakash KS and Walker MJ. Two distinct genotypes of prtF2, encoding a fibronectin binding protein, and evolution of the gene family in Streptococcus pyogenes. J Bacteriol 186: 7601-9, 2004 Rist M, Cooper L, Elkington R, Walker S, Fazou C, Tellam J, Crough T and Khanna R. Ex vivo expansion of human Cytomegalovirusspecific cytotoxic T Cells by recombinant polyepitope: Implications for HCMV immunotherapy. Eur J Immunol 35: 996-1007, 2005 Roddam AW, Spencer E, Banks E, Beral V, Reeves G, Appleby P, Barnes I, Whiteman DC and Key TJ. Reproducibility of a short semi-quantitative food group questionnaire and its performance in estimating nutrient intake compared with 7-day diet diaries in the Million Women Study. Public Health Nutr 8: 201-13, 2005 Russell RC and Kay BH. Medical entomology: changes in the spectrum of mosquito-borne disease in Australia and other vector threats and risks. Aust J Entomol 43: 271-82, 2004 Ryan PA, Lyons SA, Alsemgeest D, Thomas P and Kay BH. Spatial statistical analysis of adult mosquito (Diptera: Culicidae) counts: an example using light trap data, in Redland Shire, Southeastern Queensland, Australia. J Med Entomol 41: 1143-56, 2004 Saul A, Lawrence G, Allworth A, Elliott S, Anderson K, Rzepczyk C, Martin LB, Taylor D, Eisen D, Irving DO, Pye D, Crewther PE, Hodder AN, Murphy VJ and Anders RF. A human phase 1 vaccine clinical trial of the Plasmodium falciparum malaria vaccine candidate apical membrane antigen 1 in Montanide ISA720 adjuvant. Vaccine 23: 3076-83, 2005

85

2004–2005 Publications

Schluter PJ, Neale R, Scott D, Luchter S and McClure RJ. Validating the functional capacity index: a comparison of predicted versus observed total body scores. J Trauma 58: 25963, 2005 Schroder W, Bushell G and Sculley T. The human stress-activated protein kinaseinteracting 1 gene encodes JNK-binding proteins. Cell Signal 17: 761-7, 2005 Schroder W, Cloonan N, Bushell G and Sculley T. Alternative polyadenylation and splicing of mRNAs transcribed from the human Sin 1 gene. Gene 339: 17-23, 2004 Siskind V, Whiteman DC, Aitken JF, Martin NG and Green AC. An analysis of risk factors for cutaneous melanoma by anatomic site (Australia). Cancer Causes Control 16: 193-9, 2005 Skinner-Adams TS, McCarthy JS, Gardiner DL, Hilton PM and Andrews KT. Antiretrovirals as antimalarials. J Infect Dis 190: 1998-2000, 2004 Spurdle AB, Antoniou AC, Duffy DL, Pandeya N, Kelemen L, Chen X, Peock S, Cook MR, Smith PL, Purdie DM, Newman B, Dite GS, Apicella C, Southey MC, Giles GG, Hopper JL, Chenevix-Trench G and Easton DF; EMBRACE Study Collaborators. The androgen receptor CAG repeat polymorphism and modification of breast cancer risk in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res 7: R176-83, 2005 Stanisic DI and Good MF. Protecting infants from malaria infection: Implications for the development of successful vaccine strategies.

Global Research Network. Res Adv Infect Dis 2: 23-33, 2004 Steele TM, Frazer DM and Anderson GJ. Systemic regulation of body iron metabolism.

Aust Biochem 35: 9-12, 2004 Stephens P, Hunter C, Bignell G, Edkins S, Davies H, Teague J, Stevens C, O’Meara S, Smith R, Parker A, Barthorpe A, Blow M, Brackenbury L, Butler A, Clarke O, Cole J, Dicks E, Dike A, Drozd A, Edwards K, Forbes S, Foster R, Gray K, Greenman C, Halliday K, Hills K, Kosmidou V, Lugg R, Menzies A, Perry J, Petty R, Raine K, Ratford L, Shepherd R, Small A, Stephens Y, Tofts C, Varian J, West S, Widaa S, Yates A, Brasseur F, Cooper CS, Flanagan AM, Knowles M, Leung SY, Louis DN, Looijenga LH, Malkowicz B, Pierotti MA, Teh B, Chenevix-Trench G, Weber BL, Yuen ST, Harris G, Goldstraw P, Nicholson AG, Futreal PA, Wooster R and Stratton MR. Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature 431: 525-6, 2004

86

Suhrbier A and La Linn M. Clinical and pathologic aspects of arthritis due to Ross River virus and other alphaviruses. Curr Opin Rheumatol 16: 374-9, Review, 2004 Suphavilai C, Looareesuwan S and Good MF. Analysis of circumsporozoite protein-specific immune responses following recent infection with Plasmodium vivax. Am J Trop Med Hyg 71: 29-39, 2004 Suzuki A, Kusakai G, Kishimoto A, Shimojo Y, Ogura T, Lavin MF and Esumi H. IGF-1 phosphorylates AMPK-alpha subunit in ATMdependent and LKB1-independent manner.

Biochem Biophys Res Commun 324: 986-92, 2004 Taylor SD, Otlowski MF, Barlow-Stewart KK, Treloar SA, Stranger M and Chenoweth K. Investigating genetic discrimination in Australia: opportunities and challenges in the early stages. New Genet Soc 23: 225-39, 2004 Thompson D, Antoniou AC, Jenkins M, Marsh A, Chen X, Wayne T, Tesoriero A, Milne R, Spurdle A, Thorstenson Y, Southey M, Giles GG, Khanna KK, Sambrook J, Oefner P, Goldgar D, Hopper JL, Easton D and Chenevix-Trench G; kConFab Investigators.

Two ATM variants and breast cancer risk. Hum Mutat 25: 594-5, 2005 Towers RJ, Gal D, McMillan D, Sriprakash KS, Currie BJ, Walker MJ, Chhatwal GS and Fagan PK. Fibronectin-binding protein gene recombination and horizontal transfer between group A and G streptococci. J Clin Microbiol 42: 5357-61, 2004 Treloar S, Taylor S, Otlowski M, BarlowStewart K, Stranger M and Chenoweth K. Methodological considerations in the study of genetic discrimination: a review. Community Genet 7: 161-8, 2004 Trenholme KR, Boutlis CS, Kuns R, Lagog M, Bockarie MJ, Gatton ML, Kemp DJ, Good MJ, Anstey NM and Gardiner DL. Antibody reactivity to linear epitopes of Plasmodium falciparum Cytoadherence-linked Asexual gene 9 in asymptomatic children and adults from Papua New Guinea. Am J Trop Med Hyg 72: 708-13, 2005 Tscharke DC and Suhrbier A. From mice to humans-murine intelligence for human CD8+ T cell vaccine design. Expert Opin Biol Ther 5: 263-71, 2005 Tscharke DC, Karupiah G, Zhou J, Palmore T, Irvine KR, Haeryfar SM, Williams S, Sidney J, Sette A, Bennink JR and Yewdell JW. Identification of poxvirus CD8+ T cell determinants to enable rational design and characterization of smallpox vaccines. J Exp Med 201: 95-104, 2005

Tynan FE, Borg NA, Miles JJ, Beddoe T, ElHassen D, Silins SL, van Zuylen WJ, Purcell AW, Kjer-Nielsen L, McCluskey J, Burrows SR and Rossjohn J. High resolution structures of highly bulged viral epitopes bound to major histocompatibility complex class I: implications for T-cell receptor engagement and T-cell immunodominance. J Biol Chem 280: 23900-9, 2005 Upcroft JA, Abedinia M and Upcroft P. Rearranged subtelomeric rRNA genes in Giardia duodenalis. Eukaryot Cell 4: 484-6, 2005 Valery P, Masters IB and Chang AB. Snoring and its association with asthma in Indigenous children living in the Torres Strait and Northern Peninsula Area. J Paediatr Child Health 40: 461-5, 2004 Valery PC, Singleton RJ, Redding GJ, Torzillo PJ, Butler J, Bulkow LR and Chang AB. Bronchiectasis in Alaska Native children and Indigenous children from Central Australia.

Respirology 10 suppl: A87, 2005 Valery PC, Torzillo PJ, Boyce NC, White AV, Stewart PA, Wheaton GR, Purdie DM, Wakerman J and Chang AB. Zinc and vitamin A supplementation in Australian Indigenous children with acute diarrhoea: a randomised controlled trial. Med J Aust 182: 530-5, 2005 Valery PC, Torzillo PJ, Mulholland K, Boyce NC, Purdie DM and Chang AB. Hospitalbased case-control study of bronchiectasis in Indigenous children in Central Australia.

Pediatr Infect Dis J 23: 902-8, 2004 Valery PC, Williams G, Sleigh AC, Holly EA, Kreiger N and Bain C. Parental occupation and Ewing’s sarcoma: pooled and metaanalysis. Int J Cancer 115: 799-806, 2005 Vohra H, Dey N, Gupta S, Sharma AK, Kumar R, McMillan D and Good MF. M protein conserved region antibodies opsonise multiple strains of Streptococcus pyogenes with sequence variations in C-repeats. Res Microbiol 156: 575-82, 2005 Vu SN, Nguyen TY, Tran VP, Truong UN, Le QM, Le VL, Le TN, Bektas A, Briscombe A, Aaskov JG, Ryan PA and Kay BH. Elimination of dengue by community programs using Mesocyclops (Copepoda) against Aedes aegypti in central Vietnam. Am J Trop Med Hyg 71: 67-73, 2005 Wade TD, Treloar SA, Martin NG, Statham D and Heath AC. Monozygotic twin pairs discordant for lifetime anorexia nervosa: an exploratory investigation. Aust J Psychol 56: 127-32, 2004

Queensland Institute of Medical Research

Wainwright M, Wright MJ, Geffen GM, Luciano M and Martin NG. The genetic basis of academic achievement on the Queensland Core Skills Test and its shared genetic variance with IQ. Behav Genet 35: 133-45, 2005

Whiteman D, Clutton C and Hill D. Privacy and epidemiology: report and perspective on the NHMRC’s submission to the Review of the Privacy Act. Aust Epidemiologist 12: 4-8, Review, 2005

Wynter CV, Walsh MD, Higuchi T, Leggett BA, Young J and Jass JR. Methylation patterns define two types of hyperplastic polyp associated with colorectal cancer. Gut 53: 573-80, 2004

Walker GJ, Indsto JO, Sood R, Faruque MU, Hu P, Pollock PM, Duray P, Holland EA, Brown K, Kefford RF, Trent JM, Mann GJ and Hayward NK. Deletion mapping suggests that the 1p22 melanoma susceptibility gene is a tumor suppressor localized to a 9-Mb interval.

Genes Chromosomes Cancer 41: 56-64, 2004

Whiteman DC, Brown RM, Purdie DM and Hughes MC. Melanocytic nevi in very young children: the role of phenotype, sun exposure, and sun protection. J Am Acad Dermatol 52: 40-7, 2005

Young J, Barker MA, Simms LA, Walsh MD, Biden KG, Buchanan D, Buttenshaw R, Whitehall VL, Arnold S, Jackson L, Kambara T, Spring KJ, Jenkins MA, Walker GJ, Hopper JL, Leggett BA and Jass JR. Evidence for BRAF mutation and variable levels of microsatellite instability in a syndrome of familial colorectal cancer. Clin Gastroenterol Hepatol 3: 254-63, 2005

Wallace DF, Browett P, Wong P, Kua H, Ameratunga R and Subramaniam VN. Identification of ferroportin disease in the Indian subcontinent. Gut 54: 567-8, 2005 Wallace DF, Dixon JL, Ramm GA, Anderson GJ, Powell LW and Subramaniam N. Hemojuvelin (HJV)-associated hemochromatosis: analysis of HJV and HFE mutations and iron overload in three families.

Haematologica 90: 254-5, 2005 Wallace RA, Schluter PJ and Webb PM. Effects of Helicobacter pylori eradication among adults with intellectual disability. J Intellect Disabil Res 48: 646-54, 2004 Wallace RA, Schluter PJ, Duff M, OuelletteKuntz H, Webb PM and Scheepers M. A review of the risk factors for, consequences, diagnosis and management of Helicobacter pylori in adults with intellectual disability. J Policy Practice Intellect Disabil 1: 147-63, 2004 Walton SF, Dougall A, Pizzutto S, Holt D, Taplin D, Arlian LG, Morgan M, Currie BJ and Kemp DJ. Genetic epidemiology of Sarcoptes scabiei (Acari: Sarcoptidae) in northern Australia. Int J Parasitol 34: 839-49, 2004 Webb PM, Bain CJ and Pirozzo SL. Essential Epidemiology: an introduction for students and health professionals. Cambridge University Press. Cambridge. Pp.1-355, 2005 Webb PM, Byrne C, Schnitt SJ, Connolly JL, Jacobs TW, Baer HJ, Willett WC and Colditz GA. A prospective study of diet and benign breast disease. Cancer Epidemiol Biomarkers Prev 13: 1106-13, 2004 Webb PM, Hopper JL, Newman B, Chen X, Kelemen L, Giles GG, Southey MC, ChenevixTrench, G and Spurdle AB. Double-strand break repair gene polymorphisms and risk of breast or ovarian cancer. Cancer Epidemiol Biomarkers Prev 14: 319-23, 2005 Whiteman DC and Green AC. A risk prediction tool for melanoma? Cancer Epidemiol Biomarkers Prev 14: 761-3, 2005

Queensland Institute of Medical Research

Whitfield JB, Zhu G, Heath AC and Martin NG. Choice of residential location: chance, family influences, or genes? Twin Res Hum Genet 8: 22-6, 2005 Whitfield JB, Zhu G, Madden PA, Neale MC, Heath AC and Martin NG. The genetics of alcohol intake and of alcohol dependence.

Alcohol Clin Exp Res 28: 1153-60, 2004 Wiart A, Jepson A, Banya W, Bennett S, Whittle H, Martin NG and Hill AV. Quantitative association tests of immune responses to antigens of Mycobacterium tuberculosis: a study of twins in West Africa.

Twin Res 7: 578-88, 2004 Wicks J, Treloar SA, Martin NG and Duffy DL. New concepts for distinguishing the hidden patterns of linkage disequilibrium which underlie association between genotypes and complex phenotypes. Twin Res Hum Genet 8: 95-101, 2005 Williamson AL, Lecchi P, Turk BE, Choe Y, Hotez PJ, McKerrow JH, Cantley LC, Sajid M, Craik CS and Loukas A. A multi-enzyme cascade of hemoglobin proteolysis in the intestine of blood-feeding hookworms. J Biol Chem 279: 35950-7, 2004 Worthley DL, Walsh MD, Barker M, Ruszkiewicz A, Bennett G, Phillips K and Suthers G. Familial mutations in PMS2 can cause autosomal dominant hereditary nonpolyposis colorectal cancer.

Gastroenterology 128: 1431-6, 2005 Wright CM, Dent OF, Newland RC, Barker M, Chapuis PH, Bokey EL, Young JP, Leggett BA, Jass JR and Macdonald GA. Low-level microsatellite instability may be associated with reduced cancer-specific survival in sporadic stage C colorectal carcinoma. Gut 54: 103-8, 2005

Zhan B, Wang Y, Liu Y, Williamson A, Loukas A, Hawdon JM, Xue HC, Xiao SH and Hotez PJ. Ac-SAA-1, an immunodominant 16 kDa surface-associated antigen of infective larvae and adults of Ancylostoma caninum. Int J Parasitol 34: 1037-45, 2004 Zhang LH, McManus DP, Sunderland P, Lu XM, Ye JJ, Loukas AC and Jones MK. The cellular distribution and stage-specific expression of two dynein light chains from the human blood fluke Schistosoma japonicum.

Int J Biochem Cell Biol 37: 1511-24, 2005 Zhang WB, Jones MK, Li J and McManus DP. Echinococcus granulosus: pre-culture of protoscoleces in vitro significantly increases development and viability of secondary hydatid cysts in mice. Exp Parasitol 110: 8890, 2005 Zondervan KT, Cardon LR, Kennedy SH, Martin NG and Treloar SA. Multivariate genetic analysis of chronic pelvic pain and associated phenotypes. Behav Genet 35: 17788, 2005 Zuidervaart W, van Nieuwpoort F, Stark M, Dijkman R, Packer L, Borgstein AM, Pavey S, van der Velden P, Out C, Jager MJ, Hayward NK and Gruis NA. Activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS. Br J Cancer 92: 2032-8, 2005

Wright MJ and Martin NG. Brisbane adolescent twin study: outline of study methods and research projects. Aust J Psychol 56: 65-78, 2004 Wykes MN, Beattie L, Macpherson GG and Hart DN. Dendritic cells and follicular dendritic cells express a novel ligand for CD38 which influences their maturation and antibody responses. Immunology 113: 31827, 2004

87

Invited Lectures and Presentations

Geoff Hill G-CSF and the regulation of GVHD Optimisation of stem cell mobilsation for the separation of GVHD and GVL New methods of stem cell mobilisation Stem cell biology in allogeneic SCT Scott Burrows The Epstein-Barr virus antigen EBNA1 is recognised by a highly restricted T cell receptor repertoire: implications for nasopharyngeal carcinoma The immunogenicity of a viral cytotoxic T cell epitope is controlled by its MHC-bound conformation James McCarthy Drug resistant parasite infections: Where are we now?

Drug resistance in parasite infections Denis Moss Therapeutic opportunity for controlling nasopharyngeal carcinoma A new generation vaccine to nasopharyngeal carcinoma Epstein-Barr virus: Looking backwards, looking forwards Immunotherapeutic opportunities for controlling EBV-associated diseases Tom Sculley The EBNA- 3 gene family proteins disrupt the G2M checkpoint Alex Loukas The haemoglobin digestion pathway as a target for a hookworm vaccine.

Excretory-secretory proteins of Toxocara canis developmentally arrested larvae.

Towards a vaccine for human hookworm infection Will unveiling the schistosome transcriptome accelerate or exacerbate vaccine development?

Hookworm immunomodulatory proteins Development of hookworm vaccines David Harrich Novel pathways for HIV replication Tat is a reverse transcription cofactor Novel HIV-1 drug targets HIV replication strategies The mechanism of Tat-enhanced reverse transcription HIV-1 reverse transcription strategies Christian Engwerda Host immune responses in malaria and leishmania Anne Kelso Pathways of cytolytic T lymphocyte development New insights into cytolytic T lymphocyte development Controlling the killer within: new insights into cytolytic T lymphocyte development Regulation of CTL development and function

88

Australian Rheumatology Association Annual Meeting, Cairns, 2004 Haematology Society of Australia and NZ Annual Meeting, Melbourne, 2004 NSW Haematology Society of Australia and NZ Annual Meeting, Sydney, 2004 Hanson symposium, Adelaide, 2004

3rd Congress of FIMSA, Hangzhou ,China, 2005

6th Jakarta Antimicrobial Symposium. Indonesian Society for Tropical and Infectious Diseases Jakarta, Indonesia, 2005 Australian Society for Antimicrobials, Lorne, 2005 Asia-Pacific Conference Cairns, 2004 Indonesian National Immunology and Allergy Congress, Jogjakarta, Indonesia, 2005 Sun Yat-Sen University Cancer Centre, Guangzhou, 2004 and Second Military University Beijing, 2004 Brisbane Immunology Group conference Noosa, 2004 Indo-Australian Conference on Biotechnology and Infectious Diseases, Mannipal, India, 2005 The Eleventh International Symposium on EBV and Associated Diseases, Regensburg, Germany, 2004 Australian Society for Parasitology Annual Meeting Fremantle, 2004 American Society for Tropical Medicine and Hygiene Annual Meeting, Miami, USA, 2004 IX European Multicolloquium of Parasitology Valencia, Spain, 2004 Brisbane Immunology Group , Noosa, 2004 Australian Society for Parasitology, Fremantle, 2004 Immunomodulation by helminth parasites, Hamburg, Germany, 2005 Khon Kaen University, Khon Kaen, Thailand, 2005 St. Louis University, St. Louis, USA, 2005 Keystone Symposia, Banff, Canada, 2005 Elili Lilly Kinase Summit, Indianapolis, USA, 2005 Institut de Génétique Humaine, France, 2005 National Institutes of Health, Bethesda, USA, 2005 The Gladstone Institute, San Francisco, USA, 2005 7th FIMSA/ASI Advanced Training Course in Immunology, Adelaide, 2004 12th International Congress of Immunology Montreal, Canada, 2004 CSL Limited, Melbourne, 2004 Dr Christina Cheers Symposium, University of Melbourne, Melbourne, 2004 7th FIMSA/ASI Advanced Training Course in Immunology, Adelaide, 2004

Queensland Institute of Medical Research

Chance and necessity in the immune response

Annual Scientific Conference of the Australasian Society for Immunology, Adelaide, 2004 Development of effector and memory cytolytic T lymphocytes 3rd Congress of FIMSA, Hangzhou, China, 2005 Cytokine regulation of perforin and granzyme gene expression in Apoptosis and Immunity 2005, Palm Cove, 2005 normal CD8+ T cells Effector T cell development Postgraduate Lecture Series, The Walter and Eliza Hall Institute of Medical Research, Melbourne, 2005 Andreas Suhrbrier Kunjin replicon vectors for cancer and HIV Annual Scientific Conference of the Australasian Society for Immunology, Adelaide, 2004 Non cytopathic replicon vaccines based on the Flavivirus, Kunjin 12th International Congress of Immunology for the generation of long-lived protective CD8 T cell responses Montreal, Canada, 2004 Qin Cheng Genetic diversity of histidine-rich protein 2 and its effect on the performance of PfHRP2-based rapid diagnostic tests Michael Good The burden of malaria – developing vaccine strategies The potential for medical research collaboration Looking to the future – impact and challenges for translating biotechnology and medical research into better health The challenges of vaccine development for developing countries and Indigenous populations Looking to the future - impact and challenges for translating biotechnology and medical research into better health Challenging the malaria vaccine paradigm Whole parasite strategies for malaria vaccine development

Preclinical evaluation of a GAS vaccine candidate base on the conserved region of the M-protein Whole parasite strategies for malaria vaccination Preclinical evaluation of a GAS vaccine candidate based on the conserved region of the M protein Don McManus Molecular diagnosis of Echinococcus Schistosome Microarrays Molecular diagnosis of flatworms Brian Kay Astounding success in controlling dengue in Vietnam

Yellow fever mosquito: an old and new foe Peter Ryan Optimising surveillance for dengue vector immatures in large water storage containers in Vietnam Medical Research in Australia and QIMR dengue control research in Vietnam Mosquito and Arbovirus Research Committee and research at QIMR Multi-country study of the pupal productivity technique for the denguevector Aedes aegypti: Vietnam

Queensland Institute of Medical Research

53rd Annual Meeting of American Society of Tropical Medicine and Hygiene, Miami, USA, 2004 Asia-Pacific Conference, Cairns, 2004 National Forum, Australia’s Engagement with Asia. A New Paradigm? Canberra, 2004 The Australian Family Association, Parliament House Brisbane, 2004 Rubbo Oration, ASM 2004, Sydney,2004 Guild of St Luke, Ballymore, Brisbane, 2004 Centenary Institute of Cancer Medicine and Cell Biology, Sydney, 2004 Annual Scientific Conference of the Australasian Society for Immunology, Adelaide, 2004 Malaria Immunology Meeting, Baltimore, USA, 2005 Indo-Australian Conference on Biotechnology in Infectious Diseases, Manipal, India, 2005 CRC for Vaccine Technology Annual Conference Byron Bay, 2005 Australian Bacterial Pathogenesis Meeting “Bacterial Pathogenesis: from basic science to improved health outcomes, Couran Cove, 2005 XX1st International Congress of Hydatidology Nairobi, Kenya, 2004 Chinese National Human Genome Centre Shanghai, China, 2004 Bio2005 Conference Asian-International Molecular Biology Network (A-IMBN), Hanoi, Vietnam, 2005 Asia Pacific Forum on Tropical Health Cairns, 2004 9th Arbovirus Research in Australia and 6th Mosquito Control Assoc of Australia Symposiums, Noosa, 2004 22nd International Congress of Entomology Brisbane, 2004 9th Arbovirus Research in Australia and 6th Mosquito Control Assoc of Australia Symposiums, Noosa, 2004 Australia Post Sales Conference, Brisbane, 2004 Health and Environmental Services Region of Councils Townsville, 2005 UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Disease, Bogota, Colombia, 2005

89

Invited Lectures and Presentations

Rajiv Khanna Profiling HCMV-specific T cell response in solid organ transplant patients Preclinical studies on the development of a prophylactic vaccine for human cytomegalovirus disease Pathogenesis of Hodgkin Lymphoma – EBV in Hodgkin Lymphoma (HL) Prophylactic vaccine for human cytomegalovirus disease Novel immunotherapeutic strategies for the treatment of nasopharyngeal carcinoma T Cell perturbations during persistent viral infections Georgia Chenevix-Trench Classification of unclassified variants in BRCA1 and BRCA2 Beyond BRCA1 and BRCA2 kConFab kConFab Beyond BRCA1 and BRCA2 The annual kConfab update Chris Schmidt Metastatic melanoma responds to dendritic cell immunotherapy Metastatic melanoma: a response model

Cellular Therapies: the promise and the challenge Correlation of clinical and Immunological responses following dendritic cell immunotherapy Alejandro López Methods for the evaluation of IFN-γ production by human CD8+ T lymphocytes Direct correlation between immunological performance and clinical outcome in a DC-based immunotherapy for advanced melanoma Multiple abnormalities in dendritic cell population in patients with breast carcinoma State of the art on DC-immunotherapy and future perspectives Correlation of clinical and immunological responses following DC immunotherapy Functional characterisation of DC in patients with cancer Dendritic cells in cancer: A mechanism for immunosuppression mRNA as a tumour antigen loading strategy for DC immunotherapy Nick Hayward Interactive effects of the MC1R and OCA2 genes on melanoma predisposition phenotypes and penetrance of CDKN2A mutations Science Of Cancer: Where Are We Heading?

Nathan Subramaniam Non-HFE Haemochromatosis and Case Discussion The Liver as Regulator of Iron Metabolism Amanda Spurdle Evaluation of unclassified variants of BRCA1 and BRCA2 Breast cancer genes – which unclassified variants cause cancer?

Molecular epidemiology of endometrial cancer: The Australian National Endometrial Cancer Study (ANECS)

90

Annual Meeting of Australasian and South East Asian Tissue Typing Association, Sydney, 2004 8th International Conference on Human Leucocyte Differentiation Antigens and Annual Scientific Conference of the Australasian Society for Immunology, Adelaide, 2004 Amgen Hematology Symposium, Sydney, 2005 Indo-Australian conference on Biotechnology in Infectious Diseases, Manipal, India, 2005 East West Symposium on nasopharyngeal cancer Toronto, Canada, 2005 John Curtin School of Medicine, Canberra, 2005 Australian Breast Cancer Conference, Melbourne, 2004 Australian Society for Medical Research, Sydney, 2004 Inaugural HMRI Cancer Conference - New Therapeutics, Newcastle, 2004 Cancer Council of Western Australia, Sydney, 2004 Institute of Molecular Biosciences, Brisbane, 2004 Familial Cancer Conference, Couran Cove, 2004 8th International Symposium on Dendritic Cells Brugge, Belgium, 2004 Clinical Oncological Society of Australia 31st Annual Scientific meeting, Canberra, 2004 Dendritic Cells at the Center of Innate and Adaptive Immunity Symposium, Vancouver, Canada, 2004 Capricornia Medical Science Conference, Yepoon, 2005

Cytokine Interest Group, CICR, Princess Alexandra Hospital, Brisbane, 2005 Australian Society of Immunology Annual Meeting Adelaide, 2005 Australian Society of Immunology Annual Meeting Adelaide, 2005 GAMBRO BCT, Denver, USA, 2005 Institut Curie, Paris, FRANCE, 2005 Ludwig Institute for Cancer Research, Melbourne, 2004 ASMR Student Conference, Brisbane, 2005 Austin Research Institute, Melbourne, 2005

2nd International Melanoma Research Congress Phoenix, USA, 2004 Grand Rounds, Prince Charles Hospital, Brisbane, 2004 Annual Conference of the Gastroenterological Society of Australia, Brisbane, 2004 Institute of Molecular and Cell Biology BIOPOLIS, Singapore, 2005 Breast Cancer Information Core Satellite Meeting to ASHG Annual Meeting, Toronto, 2004 Consumer and Community Liason Taskforce Seminar Day Brisbane, 2004 Brisbane Human Genetics Society of Australasia Seminar Series, Brisbane, 2005

Queensland Institute of Medical Research

Barbara Leggett Different pathways to colorectal carcinogenesis.

Mismatch repair in clinical poractice: MSI, IHC or both?

Nick Martin Are there genes for DZ twinning?

Epigenetic factors in MZ discordance for schizophrenia The use of twins to study childhood development and behaviour QTLs for anxiety and depression using extreme discordant and concordant twins and sibs in Australia and The Netherlands.

The genetics of alcoholism.

Finding genes for cognition.

What’s hot in Australian human gene mapping.

Hunting QTLs. QTL linkage analysis for personality.

Grant Ramm Recent advances in hepatic fibrosis Iron overload and liver injury Monocyte Chemotaxis Protein-1: A candidate molecule for hepatic fibrogenesis in cholestatic liver disease” and “The role of iron-binding proteins in hepatic stellate cell biology and hepatic fibrosis in haemochromatosis Greg Anderson Mechanisms of haem and non-haem iron absorption: Lessons from inherited disorders of iron metabolism Iron, regulation, and disease Transporters and traffickers The molecular mechanisms and regulation of intestinal iron absorption Iron in the CNS Lawrie Powell New players in iron metabolism Haemochromatosis and iron overload with particular reference to Asia Haemochromatosis Lawrie Powell Genetic studies of twinning in sheep and humans Genetics of complex disease: Twins and twin families Biology of human twinning Twinning: Mechanisms and unusual cases Janelle Stirling Collaborative programmes at QIMR Partnerships in research

Queensland Institute of Medical Research

The Ludwig Institute for Cancer Research, Melbourne, 2004 Australian Gastroenterology Week, Brisbane, October 2004 11th International Congress of Twin Studies, Odense, Denmark, 2004 AstraZeneca dinner meeting: Advancing Psychosis Research in Queensland, Brisbane, 2004 Vince Hodda Memorial Oration, Mater Hospital Brisbane, 2004 XIIth World Congress on Psychiatric Genetics Dublin, Ireland, 2004 IMAG2004: International Medical Advisory Group to the Australian Associated Brewers Scientific Meeting Canberra, 2004 Australian Society for Mental Disability, Brisbane, 2004 GenomeEUtwin Scientific Meeting, Rome, 2004 International Workshop on Methodology for Twin and Family Studies, Boulder, USA, 2005 Behavior Genetics Association Annual Meeting Los Angeles, 2005 Brisbane Inter-Hospital Liver Group (BILG) Brisbane, 2004 Haemochromatosis Society of Australia - Patient Support Group, Brisbane, 2004 Melbourne Liver Group Annual Retreat, Marysville, 2005

Biometals 2004. Fourth International Biometals Symposium., GarmischPartenkirchen, Germany, 2004 Biometals 2004. Fourth International Biometals Symposium., GarmischPartenkirchen, Germany, 2004 Australian Liver Association Workshop. Australian Gastroenterology Week, Brisbane, 2004 7th Conference of the International Society for Trace Element Research in Humans, Bangkok, Thailand, 2004 World Congress on Iron Metabolism - Bioiron 2005 Prague, Czech Republic, 2005 The Arias Symposium, Boston, USA, 2004 Asian-Pacific Association for the Study of the Liver New Dehli, India, 2004 Peter Bent Brigham Hospital and Harvard Medical School, Boston, USA, 2005 Crossing-Over: Genetics and Reproductive Biology” Conference sponsored by the Reproductive Sciences Branch of NICHD, Washington, USA, 2004 Queenstown Molecular Biology Conference Queenstown, New Zealand, 2004 Combined Medical Sciences Congress Queenstown, New Zealand, 2004 Department of Psychology, Free University Amsterdam, Netherlands, 2005 Royal Brisbane and Women’s Hospital Health Care Symposium, Brisbane, 2004 One Talk: Second Aboriginal and Torres Strait Islander Health Summit, Brisbane, 2005

91

Trust Report

Mr Paul Wright – Chairman of QIMR Trust This year has seen considerable change at QIMR, proving once again that research is a dynamic and evolving industry. In my five years as Chairman of the QIMR Trust, I have been privileged to witness many encouraging developments, including a recent and ongoing venture in Hong Kong and China for the Institute’s experimental “immunotherapy” treatment against cancer affecting children as young as 7 years. This is testimony to QIMR’s status of being a world-class institute providing research benefiting communities globally. Closer to home is the Suncorp partnership supporting skin cancer research in QIMR’s Clive Berghofer Cancer Centre.

Many scientific achievements by QIMR’s 800 scientists are outlined in this Annual Report, achievements which steadily and positively impact on the health and wellbeing of us all and which will ultimately lead to reductions in the social, financial, emotional and physical costs of ill health in our community.

As the corporate dollar dwindles, the emphasis in raising funds has shifted to the individual and community base, from which many of our ardent supporters have come. QIMR is indebted to these people and they are acknowledged on pages XYZ of this report. One person who deserves a special mention is Mr Clive Berghofer. Clive’s support over the past 4 years has enabled vital human clinical trials to treat many forms of cancer to fast-track a potential new and non-invasive way of treating cancer which may ultimately benefit us all and future generations to come. For his unwavering and generous support we are most grateful.

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We are deeply appreciative to every one of our supporters who have joined us on the highway of medical discovery. Whether you gave financial contributions to our research, held a fundraising event, have left a provision in your will to QIMR, helped spread our message to others or support us through in-kind contributions, you are integral to the ongoing medical research effort at QIMR. Thank you to the QIMR Trust members and the Development and Marketing Department whose insights and persistence have resulted in significant funds raised and awareness generated which has contributed towards the purchase of vital research equipment and escalating research programs.

We hope our valued supporters will continue their relationship with QIMR and, above all, we hope that our medical research will continue to improve all of our lives. QIMR is about people who are searching for more effective treatments, diagnostic tests and vaccines to defeat diseases tomorrow but this can only be achieved with your support today.

Paul Wright Chairman

Queensland Institute of Medical Research

QIMR Trust Members 2004–2005

Mr Paul Wright FAIM FAIBF FAICD Mr Paul Wright has combined banking, health, hospitality and consulting industries in a career which has encompassed over twenty five years in senior executive management with a breadth and depth in leadership roles. He has been General Manager Qld and NT of Medical Benefits of Australia Limited and provided executive services as General Manager of The Brisbane Club.

Paul has also been a company director for more than twenty years and has served as Chairman/President of The Australian Institute of Management and The Royal Flying Doctor Service. He is currently Chairman of The CyberInstitute Pty Ltd, The Queensland Institute of Medical Research Trust and Phoenix Eagle Company Pty Ltd. Other current Board appointments include QIMR Council, The Royal Flying Doctor Service, PQ Lifestyles Pty Ltd and Queensland Fruit and Vegetable Growers Limited.

Mr John Garnsey FAIA (Dip) The Trust benefits immeasurably from Mr John Garnsey’s accomplishments in strategic marketing and his knowledge of both national and international advertising campaign development. He is former Chairman and Managing Director of Garnsey Clemenger Advertising Agency and past Chairman of the Advertising Federation of Australia. Mr Garnsey chairs the QIMR Marketing Committee.

Mr Rodney Wylie OBE BA FCA FAICD DUniv(Griffith) Mr Rod Wylie is a Brisbane-based Chartered Accountant with substantial experience in investment, company management and corporate governance issues across a wide range of organisations, in many cases with nationwide and international activities. He has been involved through Board/Council membership in the administration of a number of professional and community non-profit groups. Mr Wylie chairs the QIMR Investment Committee and is a member of the QIMR Finance and Audit Committee

Mr Ian Manly MBA Mr Ian Manly has extensive experience in business management and corporate development. He is the Managing Director of First 5 Minutes, a company providing fire and emergency procedures and training. Mr Manly is a member of the QIMR Investment Committee.

Queensland Institute of Medical Research

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QIMR Trust Members 2004–2005

Mr Richard Alexander Joel AM MAICD Mr Richard Joel is principal of Richard Joel and Associates Strategic Consultants. He was previously Chief Executive Officer of the Office of Economic Development for the city of Brisbane for 17 years and prior to that, Managing Director of the diversified public company Walter Reid and Company Ltd for 10 years. He has been a Director of several public and government companies and is currently a Director of Queensland Railways.

Richard has had extensive experience in marketing and public relations both in Queensland and overseas and has undertaken a number of business courses in these areas. He was awarded an Order of Australia and the 2000 Centennial Medal for services in promoting economic development in Brisbane.

Ms Jane Seawright BA LLB(Hons) MBus (Marketing) AAIM Ms Jane Seawright is a lawyer with extensive experience in marketing and strategy who established a freelance marketing consultancy, Seawright Consulting, in 2000. She has held the position of Independent Chair of the Queensland Furnishing Industry Superannuation Trust since 1990 and is also a Law Society-accredited mediator. Ms Seawright is a member of the QIMR Marketing Committee.

Ms Margot de Groot LLB GradDip(Legal Practice) Ms Margot de Groot is the Managing Partner of de Groots Wills and Estate Lawyers, a Notary Public and former Director of Energex Retail Pty Ltd and Queensland Law Foundation Limited. Mrs de Groot is a member of the QIMR Marketing Committee.

Mr Bruce Phillips DipCom Mr Bruce Phillips has extensive experience in the field of investment advice with some 40 years of active involvement in the Securities Industry. He is a former member of the Australian Stock Exchange Ltd, a past Chairman of the Brisbane Stock Exchange and is a Fellow of The Securities Institute of Australia. He has been a Director of The Bank of Queensland Limited since November 1996 and is a consultant to ABN AMRO Morgans Limited. Mr Phillips is a member of the QIMR Investment Committee and the QIMR Finance and Audit Committee.

Ms Patricia McCormack BA (Psych and IR) Ms Patricia McCormack is a highly regarded People Management professional with extensive experience in all facets of Human Resource Management.

She established People Focus in 2002 with the aim of providing HR services specialising in organisation development and human resources management.

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Queensland Institute of Medical Research

Donors to the Institute

Visionary (over $50,000) ABC Learning Centres Callaway Golf Hi-Lite Pro Am Australian Rugby Union (Tom Slack Dinner) Berghofer C Carlton Crest Hotel Brisbane Estate of Gwen Cameron Estate of Kathleen Jenkins Estate of Viva Busteed Lee I Macquarie Bank Foundation Pratt Foundation Suncorp Suncorp Ride 4 Research Yu Feng Pty Ltd Wantz Committee Platinum Friend Supporter ($20,000 - $49,999) AMAQ VMO Committee Boyd D (Bell Legal Group) Bryan R & K Champers Ball (Kathy Bourke) Efron Family Foundation Ltd Estate of Margaret Wilson Estate of Elsie Squares Gibson BC & MJ Hair-Raising Cure Intro International Jen Retail Properties Limited Jupiters Casino Community Benefit Fund Marina Mirage Fashion Gala Designer Dinner Qantas Airways Queensland Property Foundation Roy & HG Luncheon Suncoast Social Dancers Association Trust Company of Australia Limited Zonta International (Gold Coast) Art Auction Benefactor ($10,000 – $19,999) ANZ Trustees Australian Rotary Health Research Fund Bored Housewives Luncheon BT Investment Management Pty Ltd Busdrivers’ Australia Carlton & United Beverages Christensen P (Gayler Cleland Towne) Conrad Treasury Bachelor Auction Early Risers’ Breakfasts Estate of Gregory Hill Estate of Kathleen Joan Kingsbury Estate of Norah Jenkins Estate of Thomas Ruddell Estate of Walter Bell Taylor Fitton Charity Stallion Tender Francis GD & IA Fung J Gandel Charitable Trust Gow H Hayes K & E Hicks BB Hornibrook Buslines

Queensland Institute of Medical Research

Knight LM McKay B & E Ongley M Ongley N Peden M Queensland Rail Rotary Club of Bardon Rueben Pelerman Benevolent Foundation Scuba-Doo International Pty Ltd Sheraton Hotel Melbourne Cup Day Thynne G & K W FM Motors Pty Ltd Zonta Club of Gold Coast Gold Friend Supporter ($5,000 - $9,999) All British Classic Car Club ANZ Qld Community Foundation (13974505) Arthur Earle Youth Foundation Limited Bill & Lesley Freeman Jazz at Kianga Brisbane Advertising Association Inc Bruce Gleeson Solicitor Coles M Cook B (Sunflower Queen) Cory Charitable Foundation DK Marketing Pty Ltd English JB & DP Estate of Barbara Dalton Estate of Gloria May Jean Estate of HC & SM Robjohns Estate of ML Morgan Estate of Nonna Kras Fairweather F Fitton Insurance Charity Race Day Fitton Stallion Tender Gibney T Green JE Grigg B Hillhouse Burrough McKeown Holzapfel D & Holzapfel U Indooroopilly Golf Club McKay B Mott M Mullen C O’Boyle D Quantum Scientific Pty Ltd Riverside Centre Charity Golf Day Stevenson B Shop Distributive & Allied Employees Association Syme A Watson B & J Wesley Clinic For Hematology & Oncology Witchery Wylie R Silver Friend Supporter ($1,000 - $4,999) Acton CR Alleway G & C Andrew B Apex Club of Meandarra Austin S Back R

Barnett LR Blackburne Developments Pty Ltd Boomerang Paper, A Division of CPI Group Ltd Bradley Services Brady K Brew M Cameron I Celebrity Closet Clearance Coleby R Comino G & M Conrad International Treasury Casino Cowlishaw DO Curnow B Custance R Dalley HE Davis C Deloitte Drescher S Driscoll K (National Homes Pty Ltd) Duckwitz L Duguid E Earle Haven Community Church Fellowship Egerton M (Fisher Adams Kelly) Estate of Mavis Jarrott Estate of Thomas & Coral Williams Flecker PO Former Origin Greats Ltd Gates J Goodtimes Photography Golf Day Grafton Pony Club Gram Engineering Pty Ltd Hale JA Happy Face Cent Auction Haseler JM Hawken B Healthy Slimmers - Mitchelton Heck B & P Henderson Foundation Herron K & J Horton Park Golf Club Maroochydore Inc Huybers EF Infinity Five Inner Wheel Club of Brisbane South Inc Jackson RAS Jameson Charitable Foundation Karen Phillips Corporate Communications Kedron Wavell Ladies Auxiliary KedronWavell Exservice Women Kennedy N Lam S & Yau V Law B & J (ESS Engineering Services) Lendich V & A Leonard C & S Lindsey J Lioness Club - Innisfail Loughnan A & J Lovell WT & NB Macmillan J MacNeill J Maleny Contract Bridge Club Marina Mirage Boys Day Out Maryborough City Council

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Donors to the Institute

McCann Erickson Advertising McDonald K Meehan AM Mermaid Beach Bowls Club Inc Miano T & E (Volare Restaurant) Morris A Mt Coolum Charity Golf Day Nambour Golf Club Inc. National Seniors - Bribie Island National Seniors Association - Nambour National Seniors Association Caboolture Branch Old Rockers Get Together Onecard Australia Pty Ltd Opala R Order of the Eastern Star - Brisbane District Grand Chapter Ozanne ST & DE Foundation Paradise Point Bowls Club Inc Parsons K Penny Ridge Silk Stocking Ladies Race Day Perel ID Phillips B Pine Rivers Memorial Bowls Club Poli LM Price JB Purcell P QCWA - Inglestone Branch Queensland Community Foundation Quinn D Quota International of Beenleigh Inc Redman J Refrigerated Warehouse & Transport Assoc of Australia Ltd Remote Area Nurse Robertson HF Robinson Media Rotary Club of Blackwater Rotary Club of Noosa Schwarz N Sebel Suites & Quay West Hotels Seeleither D Slaughter J Smith F & V Smith S Southport Worker’s Club Stein E Stewart JM Stormonth M Talamini B (Queensland Vintage Vehicle Association) Throp E Tomlinson F Tremewen I (Tremewen Water Colour + Design) Turner G & Y Tweed Links Music Club United Medical Insurance Ltd USM Events Van Klinken A Villa Luncheon Wassman RC

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Webb PG Welsh P Wesley Medical Centre Wheeler E White Foundation Limited Whittaker P Wynn RG Zaccari F Zonta Club Of Blackall Range Bronze Friend Supporter ($500 - $999) Aitchison D & N Andrews P Australian Hibiscus Society Inc - Buderim Branch Australian Society For Medical Research Austmel Pty Ltd Badke A Bailey D Baird D & N Baker RE Bale S Ball P Barrett J (Urban Executive) Beardmore HA & JM Blackwell E Boult L Bourke L Brisbane Marketing Pty Ltd Brunswick Valley Cancer Action Group Bunnings Browns Plains Burgess GT & LB Burleigh Heads Uniting Church & Friends Busta Pinata Calamvale National Seniors Carlton & United Brewery Campbell IG & R Caniglia D Carter DH Channel 9 Chen LY Christopher B (Johnson Screens) Clark DJ Clark Y Collinson RA Comserv (No 1643) Pty Ltd Conroy B & J Cox C Davis C (Chinchilla Rotary Club) Day GL de Bie V Drummond GJ & VJ Ducquet G Easton N Eggar RC & JG Eisenberg IB English K English L Essex J (Busta Pinata) Fawcett W Firkins H Furnival C & I

Future Floor Services Gac M Gannon T Gill J & M Glebe Road Uniting Church Gold KA & GM Good M Goodtimes Network Photography Gordon D Grano S Gray L Grimmer K Groh C Hallett K & M Hancock AB Harwood RS Hawthorne P Hayman K Hoey EM Holmes C Hughes M Hurd S Hutchinson Builders Indooroopilly Garden Club Inc Island Brisbane River Cruise Committee J C Liao Family Trust Jackson P James R & P Johnsson DK Jones L & L Kawana Senior Citizens Inc Kelso A Kester M (Syngenta Japan K K) KG Transport Services Kone Elevators Lake S (GBST) Larsen R & P Lauder J & P Leighton Holdings Limited Les Cheveux Hair Artistry Logan D Lumley JW May ME McComiskie RJ & CM McLaren D & L Mirvac Hotels Murray M Murray J National Seniors Association – Hervey Bay National Seniors Association - Redcliffe National Seniors Association - Warwick National Seniors Association - Wynnum Manly Branch National Servicemens Assn. (QLD) Inc Caboolture And District Branch New Age Productions - The Goddess Trust New Caledonia Grazing Co Nickelson Transport Nicklin J O’Brien D O’Connor B Order Of The Eastern Star - Moreton Bay

Queensland Institute of Medical Research

Chapter No 152 Parker Family Bequest Peacock RL Perpetual Trustee Company Ltd Perrin L Philipson M Phillips R Phillips S Potts & Family JG & PMP (Clanwilliam Pty Ltd) Powter Trustee for E & S Powter S Prads M Queensland Railway Institute Ray White Surfers Paradise Riethmuller C Rose P Royal National Agricultural & Industrial Association Rutherford L-G Sandling T Sarafian K Schramm M Schuster R Serco Pty Ltd Sharpe FA Sheeran L Shepherd A Shinners R Sim L & S Simpson M Smallegange B Smith BH & JM Smith L Southern Qld Women’s Auxiliary Stephens M Stephenson D Stonestreet’s Coaches Pty Ltd Stoney HM Straney A Strathlea Pty Ltd Sunnybank Masonic Lodge No 264 Uglq Synergy Executive Sourcing Syngenta China Team Management Systems Thomas Tsang Associates Tindle R & E Tobias J (Women at Work) Toowoomba Golf Club Women Members Top End Partnership Trisco Foods Turner G Ward F (Ruby & Company) West NR Whitney AI Wong MC Woodcock A & I Wright G & D Xu D Zonta Club of Blackall Range

Queensland Institute of Medical Research

Friends ($200 - $499) Abel K Accenture Pty Ltd Action Concrete & Asphalt, Drilling & Sawing Adam G ADF Group Aland RW Alberts V Alcorn N Alkin JC Allanna Plumbing Services Allen LH Allison P Ambrose J Anderson K Anglican Parish of Kilcoy Anstey J Armstrong B & L (Armstrong Excavation) Armstrong YC Arrowdynamics Arthur G & J Audrey Page & Associates Austin CN Australia Meat Holdings Australia Post Bach T Barnett JG & MC Baronio PF & T Bartlett D Bartrum G Basei G & N Batt Property Baxter E Baylis AM Bechly C Benny MP Berkley Group Berry E Berry K Bevan EF Big Country Machine Tools Billing W Bird V Bjorklund D Body Bronze Bray Park State High School Staff Brereton D Brian O’Connor Real Estate Brickhill LW Broadbeach Dental Centre Brooks EL Brown C Bruderlin K Bruggy WA Burns LR Burrough M Cameron A Campbell A Carlton & United Breweries Carlyon C Carseldine ML

Carter B Carter M Carter R & L Catholic Womens League - Banyo Catholic Womens League - Kawana Waters Centenary Hire Chatfield V Chippendale F & ME Christie HS Christopher MRA Clark WB Clarke L Clendinnen FJ Cloherty L Cock WJ Cockram F & J Colvin M Comans L Comerford J Community Friendship Centre Cook G Cooke R A & J A Cooper E Cornell L Courtice & Neilsen Solictiors Cox G & E Crombie M Crosthwaite MA Cullen R & V Curragh Queensland Mining Pty Ltd Dawes D De Vryer R & H Deloitte Touche Tohmatsu Dillon J Disher Real Estate Donnan DM Dowling R Drager Medical Australia Draman J Drizza-Bone Dunn B Dustow E & J Dwyer M Dyer B Eadie WH Earl B Eaton D Edmeades R & A Eeles GA Ellis J & J Elson V Estate of Jill Bain McAdam Evans and Hearn Farley P Ferguson M & L Finn P Fischle J Fitch ES Fookes AJ Foote GM & BM Formula Interiors Forsyth S

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Donors to the Institute

Foxton HAB & AM Francis BM Frank Carroll Solicitor Fraser EH Freeman IB Fry GC Fuery TE Fulton-Kennedy & Family B Galley D Galluzzo S Gannon J Garson CW Gateway Properties Gaythorne Ladies’ Bowling Club Inc Geisler KA Gibb N & A Gibson M GIO Social Club Girl Guides Assoc Qld Aust - Stafford Trefoil Guild Glasgow M Globenet Travel Goldilocks GrainCorp Operations Limited Grant J Granville P Greenup RB & MC Grigg F & E Guest C Guest FJ Guilford P Guy AJ Gynther M Hanger B Hannaford Rose & Geranium Club Harkin S Harris K Hartland RD Harvey HL Harwood K Hawes RB & AM Hay V Heart Support Australia - Ipswich Branch Heaton Electrical Hemming A Herron Todd White Hill D Hill K Hill O Hillier Engineering Services Hoan L Hockings E Hockings V Hollamby J Hollis P Holloway V Holmes D Honeywell Limited Hughes RE Humphrey P Hurcom P Hyde RE

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Hyperion Asset Management Ilett GB Ingles GA Institute of Chartered Accountants Ipswich Hospital Nurses Assoc Inc J J Richards & Sons Pty Ltd J W Maguire Medical Pty Ltd James Frizelle’s Automotive Group Pty Ltd Jenkinson NA & PE Jobling WJ Jones PB & MG Jordan KE Kavali M & S Kawana Quilters Keates C Kelly B Kelly P Kentish E Keown B Khoon GK King R Kirby A Kirby L Kreis B (Nayrb Nominees) Kuhn Steel Fab Pty Ltd Ladner A Lambert L Lancaster V Larbalestier K Lardercon Pty Ltd Larkin W Lawler S Lawrence JM Learmonth JH Legacy Widows of East Brisbane Lekias D Lewis R Little JE Living Chose Retirement Village Lockwood J & R Long A Low H Lyle Lovelock & Associates MacDonald K Mackay D MacKellar M MacQuarie Goodman Industrial Trust Mann J Marina Mirage Marshall J McCready SP McCutchan A McEwan D & G McGavin MH McHenry T McInally B McKay R McKay RJ & MJ McMillan L McVeigh M Mei-Li C Meritplan Pty Ltd

Miano T & E Mickan RC Miller N Miller VM Mitchell DE & Mitchell R Mitchelton Day HSF Moody WG Morris K Morris W Moses P Mount Alvernia College Staff Club Muir C Murray K Musgrave KI & EW National Seniors Association - Gympie Nelson S Network Ten New South Wales Treasury Corporation Newtown State School Novartis Pharmaceuticals Australia Pty Ltd Nundah Fellowship Nundah Industries Pty Ltd Oaks Resorts & Hotels O’Brien D & G O’Brien H O’Hara B & L Oliver S O’Meally G O’Neill A O’Neill L & B Order of the Eastern Star - Coolangatta Chapter Packett J Parker J Parry E Parry-McKitrick M Paxton J Pearce GV Perham J Perpetual Investment Management Pershouse C Pipe-Jones R & J Pitkanen A Plummer A Polley JV Ponti P (Carswell & Company) Poole D Porter C Potent J Poulsen GP & DM Powell JG PRD Nationwide Price C Price DJ Price HD & A Probus Club of Southport Incorporated Public Trustee of Queensland Pukall D & K Purcell L Purtell D QCWA - Norwin Branch QR1 Brisbane Branch

Queensland Institute of Medical Research

Quaid D Queensland Country Women’s Association Queensland Rail Queensland XXXX Goldies Rugby Club Quill J & L Quinn & Scattini Rains C & MJ Rapcivic Contractors Pty Ltd Read P Redbank Goodna Lioness Club Redlands Engines Pty Ltd Reed FC Regnart AL & OS Reid C Reid M Reordan R Rice B Richardson G Richardson K Riverside Industrial Maintenance Pty Ltd Riverside Newsagency Robbins B Roberts GE Robinson W Robinson W & A Rogers K Rollason BM & DR Rose E Rotary Club of Mitchelton Rudder M Russell K Russell R Sandgate Golf Club Associates Say AH Scheele J & J Schonfeld D Schulte M Scots College Campdraft Committee Scott C Scott RW Seaman R Seccombe J Selwood RM Serafin O Shaw A Sherlock G Shields J & R Smeralda S Smith BP & BL Smith C Smith G Smith I Smith J & V Smith K Smith M Smith P Smith R & N Solley E Solomon I Southern Cross Ford Spencer R & M Spiers P

Queensland Institute of Medical Research

St Georges Anglican Church St Monica’s Soup & Sandwich Group Statham H Stendrup VA Stevens D Stevens M & M Stewart DC Stuart M Sullivan D Sunnybank Thin Thinkers Swart M SweetPea Corporation Pty Ltd Syngenta Seeds Tapscott B Templo A & C Tempo Services Thomas AA Thomson I & D Thynne N Tice M Tilse G Timothy K Tobler G Todd V Tompkins P Toohey AB & JW Toombs P & C Townsend I & I Tree S Tuesday Embroiderers Unwin M Vance V Vandeleur P & ME Vandeven L Venzke N Verity N & M Wagner Investments Pty Ltd Walsh Halligan Douglas Wambo Shire Council Wanless Mr & Mrs Warburton S Ward MJ Wardan E Watson A Watson B Watson K & D Weatherstone J Webb K Webber BR & JC Weight Reduction Club of Lawnton Wenck WN Whitbread R White N L & P R Wilkey I Willcocks M Williams D Wilson K Wilson KJH Wilson HTM Wilson Parking Winkler JA Woodhead K

Woolley A Yarrabee Coal Company Pty Ltd Zar Mortgage Brokers Zielke’s Transport Zinns A

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Staff 2004–2005

DIRECTOR M F Good BSc(Med) MBBS(Hons) PhD MD DSc FASM FAFPHM FRACP(HON) FAIM Deputy Director A C Green MBBS MSc PhD Secretary and Chief Operating Officer M J Staley MSc GMQ MBA FAIM MAICD Assistant Directors A W Boyd BMedSc(Hons) MBBS PhD FRACP University of Queensland M F Lavin BSc(Hons) PhD University of Queensland Executive Secretary to Director J Chapple Administrative Support T Checkley Communications Officers : R Lynch BSc MPH (to Feb 05) K Green BSc(Hons) PhD (to Dec 04) J O’Keefe BAppSc DipBusComm INFECTIOUS DISEASES AND IMMUNOLOGY DIVISION Division Chair : J McCarthy Bacterial Pathogenesis K S Sriprakash BPharm MPharm PhD M Binks BSc C Denham BSc(Hons) D McMillan BSc(Hons) PhD J Shera BSc(Hons) T Tran BSc (Hons) Bone Marrow Transplantation G Hill BHB MBChB FRCPA FRACP MD T Banovic MD MmedSc H Bofinger BAppSc(Hons) P Bunn A Burman BSc PhD A Don BSc(Hons) R Kuns BSc(Hons) K MacDonald BSc(Hons) MSc PhD N Odorico BSc(Hons) V Rowe TechCertAnimalLabSc AdvCertAppSc Cellular Immunology S R Burrows BSc PhD M Bell BSc(Hons) J Burrows BSc GradDipTeach S Silins BSc(Hons) PhD Clinical Tropical Medicine J McCarthy MBBS FRACP MD Royal Brisbane and Women‘s Hospital K Andrews BSc(Hons) PhD N Lee BBiotech(Hons) L Melville BSc BA C Pasay BS MSc PhD EBV Biology D J Moss BSc PhD M Corban BBiol MBiol P Crooks BSc(Hons) J Davis BSc(Hons) PhD J Duraiswamy MSc BVSc PhD K Harej RN L Heslop BBiomedSc L Morrison CBLT R Moor BAppSc(Hons) A Nehring BNurs BSc(Hons) M Sherritt BSc(Hons) PhD (to Sep 04) D Tscharke BSc(Hons) PhD Y Woo BSc (Hons) PhD EBV Immunology I S Misko BSc(Hons) PhD S M Cross BSc(Hons) MSc DipEd K Green BSc(Hons) PhD (to Dec 04)

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EBV Molecular Biology T B Sculley BSc(Hons) PhD M Buck DipMedTech K Krauer BSc PhD (to Dec 04) Helminth Biology A C Loukas BSc(Hons) PhD S Kosmala BSc(Hons) M Pearson BSc MSc M Smout BSc(Hons) M Tran BSc GradDipClin BioChem PhD HIV Molecular Virology D A Harrich BSc PhD A Apolloni BSc PhD C Harrich RN BSc(Nurs) L Meredith BSc(Hons) D Warrilow BSc(Hons) PhD N Willemsen BAppSc(Hons) Immunology and Infection C R Engwerda BAgrSc PhD F Amante BSc(Hons) PhD K Clark BSc(Hons) A Stanley BSc(Hons) PhD Immunoregulation A Kelso BSc(Hons) PhD A Baz BChem PhD K Buttigieg BBioTech P Groves BAppSc M Janas BSc(Hons) PhD (to Feb 05) N Kienzle BSc PhD S Olver BSc(Hons) Immunovirology A Suhrbier BA(Hons) PhD I Anraku BSc(Hons) G Darnell BAppSc GradDipBiotech MAppSc PhD J Gardner BAppSc D Hoang-Le BSc(Hons) Thuy Le BAppSc GradDipBiotech M Linn MBBS PhD T Pirayesh BSc W Schroder BSc(Hons) PhD Malaria and Scabies D J Kemp BSc(Hons) PhD K Anderson CBLT K Fischer PhD M Ortega BSc (to Dec 04) A Topping BSc(Hons) K Trenholme BSc MSc PhD Malaria Biology D L Gardiner BAppSc PhD Malaria Drug Resistance and Chemotherapy Q Cheng MBBS MSc PhD Australian Army Malaria Institute M Chavchich BSc MSc K Gresty BSc(Hons) D Krause BSc(Hons) PhD S McLeod-Robertson ADCLT J Peters BAppSc Molecular Genetics P Upcroft BSc(Hons) PhD L Dunn BSc(Hons) PhD J Upcroft BSc(Hons) PhD Molecular Immunology M F Good BSc(Med) MBBS(Hons) PhD MD DSc FASM FAFPHM FRACP(HON) M Bailey BSc(Hons) PhD (to May 05) M Batzloff BSc(Hons) PhD J Dyer BSc(Hons) J Hartas BAppSc J Heise-Seabrook BBiotech(Hons) MF Ho BSc(Hons) M Hocart BSc(Hons) PhD X Liu BMed MMedSc V McPhun BSc MSc C Olive BSc(Hons) PhD

M Pandey BSc MSc PhD A Pinzon-Charry MD PhD K Potter LabTech D Stanisic BSc(Hons) PhD (to Oct 04) S Williams BSc(Hons) MSc PhD (to Oct 04) M Wykes BSc(Hons) PhD H Xub BMed MMed PhD Y Zhou B Med DipAppSc Molecular Parasitology D P McManus BSc(Hons) PhD DSc M Duke AssocDipFarmMngmt G Gobert BSc(Hons) PhD M Jones BSc(Hons) PhD J Li BPharm PhD (to Apr 05) Y Li MD PhD P Sivadorai BSc(Hons) (to Feb 05) L Zhang BMSc MMSc PhD W Zhang BSc PhD Mosquito Control B H Kay BSc(Hons) PhD M Breitfuss BSc(Hons) PhD (to Sep 04) P Fraley T Hurst BSc(Hons) PhD S Lyons BSc (to Dec 04) K Marshall L Perkins BSc(Hons) PhD P Ryan BSc(Hons) PhD Tumour Immunology R Khanna BSc MSc PhD G Connolly BSc(Hons) (to Nov 04) L Cooper BAppSc T Crough BSc(Hons) U Dua BSc MBiotech C Fazou BSc(Hons) MSc (to Nov 04) M Gandhi MBChB MRCP MRC Path PhD L Jiang BMed MMed PhD E Lambley BSc(Hons) (to Nov 04) M Rist BSc(Hons) PhD C Smith BSc(Hons) PhD J Tellam BSc MSc PhD N Webb BSc GradDip ClinBioChem J Weiss BSc CANCER AND CELL BIOLOGY DIVISION Division Chair: KK Khanna Cancer Genetics G C Trench BSc(Hons) PhD J Arnold BSc(Hons) PhD J Beesley BSc(Hons) X Chen BMed H Holland BHlthSc(Hons) BA L Kelemen BSc (to Dec 04) J Kerr BSc(Hons) A Marsh BSc(Hons) N Waddell BSc(Hons) PhD Cancer Immunotherapy C W Schmidt BSc(Hons) PhD M Arico GradDipAppSc BSc (to Jun 05) K Ellem BSc(Med) MBBS PhD X Huang BMed PhD C Lanagan BBiomedSc(Hons) N Martinez BSc(Hons) PhD L O’Connor AssocDegAppSc Cell Therapy A J Nicol MBBS FRACP FRCPA PhD University of Queensland T Hagi BSc MSc (to Jan 05) A Tazbirkova MD (to Aug 04) A Westcott BSc(Hons) (to Dec 04) A Yamaura BMed MMed (to Dec 04) Dendritic Cells and Cancer J A Lopez MD Human Genetics N K Hayward BSc MscQual PhD L Aoude M Auret BSc(Hons) PhD J Bowden (to Jan 04)

Queensland Institute of Medical Research

R Duncan BAppSc(Hons) N Irwin BSc(Hons) (to Jan 05) K Loffler BHlthSc BSc(Hons) PhD D Nancarrow BSc MscQual PhD J PalmerRN L Parsonson (to May 05) S Pavey BAppSc(Hons) PhD P Schultz M Stark BAppSc(Hons) G Walker BSc GradDipClin Bio chem MScQual PhD S Walsh Leukaemia Foundation A W Boyd BMedSc(Hons) MBBS PhD FRACP University of Queensland J Butler MBBS (to Jan 05) J Carter BAppSc(Hons) K Chen BSc(Med) J Cox BAppSc GradDipBiotech B Douglas MSc(Hons) M Down BSc GradDipSc (to Jan 05) S Duffy BSc(Hons) N Herath BSc(Hons) PhD J Lickliter MBBS PhD J McCarron AssocDipAppSc J Reeder DMLT MMedSc M Scott BSc(Hons) (to Apr 05) F Smith BAppSc M Spanevello BAppSc(Hons) PhD B Stringer BMedSc MBBS PhD J Tid-Ang BSc(Hons) Membrane Transport N Subramaniam BSc MSc PhD P Lusby BSc (Hons)(to Mar 05) L Summerville BSc GradDipClin Biochem D Wallace BSc(Hons) PhD Molecular Cancer Epidemiology A B Spurdle BSc MSc PhD S Arnold BSc(Hons) M Barker BAppSc MSc G Birney BSc (Hons) D Buchanan BSc(Hons) L Butterworth ADCLT S Healey BSc DipEd BAppSc L Jackson BSc P Lovelock BSc(Hons) PhD R Magson BSc M Newman M Walsh BSc J Young GradDipBiotech MAppSc PhD QCF Transgenics G F Kay BSc(Hons) PhD S Greco BSc P Keith BSc MPhil M Martinez DipAssSc A Mould BSc(Hons) PhD I Tonks BSc(Hons) PhD Radiation Biology and Oncology M F Lavin BSc(Hons) PhD University of Queensland O Becherel PhD G Birrell CBT MMedSc PhD P Chen BSc MSc PhD A Farrell NCEA CertAppBiol M Gatei BSc PhD N Guven BSc MSc PhD A Kijas BBiotech PhD K Kneebone BAppSc (to Nov 04) S Kozlov MSc PhD J Luff CVetNurs/AnCare C Peng MMed PhD N Rundle MSc(Hons) PhD S Scott BSc(Hons) PhD (to Apr 05) H Snelling BSc MSc (to May 05)) T Vaughan BSc (to Feb 05) R Woods BSc(Hons) PhD

Queensland Institute of Medical Research

Royal Brisbane and Women’s Hospital Foundation B A Leggett MBBS(Hons) MD FRACP Royal Brisbane and Women’s Hospital C Bond BPhysio MMolecBio M Brett (to Jun 05) J Chia BBiotech(Hons) S Cozzi BAppSc(Hons) B Cronin BLaws BComm (to Dec 04) K Cusworth BSc (to Dec 04) R Karamatic BSc(Hons) (to Dec 04) E Pelzer BA BAppSc T Pike BSc(Hons) ( to Apr 05) R Price CertVetNurse LabAnimalTechCert J Robinson BSc(Hons) PhD (to Mar 05) L Simms BSc(Hons) (to Nov 04) K Spring BSc PhD J Turner BMedSc PhD (to Aug 04) V Whitehall BSc(Hons) PhD Signal Transduction K K Khanna BSc MSc PhD E Bolderson BSc(Hons) PhD M Fabbro BSc(Hons) PhD K Hobson BSc(Hons) D Richard BSc(Hons) PhD M Shariff BSc (Hons) S Tsvetanov MSc PhD A Urquhart BSc(Hons) PhD D Young BSc(Hons) PhD POPULATION STUDIES AND HUMAN GENETICS DIVISION: Division Chair: G Anderson Cancer and Population Studies A C Green MBBS MSc PhD B Alexander RN BNursing P Ashover RN BNursing (to Apr 05) J Bain C Baxter BA S Brown RN BA M Connard BSc(Hons) T Corish RN H Croy BSc BNursing M Davis MD M Dunks RN R Dutton L Green RN K Harrap BInfoTech (to Aug 04) E Herron RN DipOccupHlthNurs (to Dec 04) M Hughes BS MMedSc K Ibiebele BScClinDiet MPHSocSc PhD L Jackman BSc(BusAdmin) S Jordan MBBS (Hons) FRACGP DRANSCOG GradDipEpidem D Lincoln BSc(Hons) MBiostats V Logan C Loos BAppSc T Luong AssocDipArts/Photog M Malt BBus EN M Martin RN (to Aug 04) K Martin RN BHlthAdmin J Mayhew A McMurtrie RN BNurs M Merritt BSc(Hons) E Minehan RN S Moore RN BHlthSc MPH P Moser S Mott BSc RN R Neale BVSc PhD S O’Brien BNurs MPH S O’Keeffe BAppSc RN N Pandeya BSc GradDipAppSc MMedSc S Perry DipAppScNurs BAppSc Nurs MEnvirCommHlth BEnvirHlthSc C Phillips (to Dec 04) D Purdie BSc(Hons) PhD (to Jun 05)

K Quinn J Ramsden B Ranieri D Roffe N Richmond T Sadkowski V Siskind L Terry

RDT RDP

RN BAppSc (to Dec 04) BSc BSc PhD RN BHlthSc MHlthPlan MHlthLaw J Thomas BHlthSc P Valery BMed MPH F Walker RN A Ward RN (to Mar 05) P Webb MA PhD S Webb BNursing J White RN D Whiteman BMedSc MBBS(Hons) PhD Genetic Epidemiology N G Martin BSc(Hons) PhD S Allerton BPsych(Hons) (to Aug 04) L Anderson BA(Hons) L Barnes RN P Barton A Baxter BAppSc M Baylart H Beeby BSc(Hons) A Birley BSc MSc PhD V Bradford BPsych (to Jan 05) S Brimstone BA(Hons) MBus Med J Brodie S Burgis BPsych(Hons) M Caffrey N Cloonan BSc (Hons) A Casal R Cicero BA H Clarke T Coates BA GradDipEarlyChild J Cochrane BBus L Connelly N Cross BA(Hons) T De Dassel BSc(Hons) M De Nooyer BPsych(Hons) P Dickson BSc(Hons) D Duffy MBBS PhD H Egan DipBusMngmt T Eichmann BSc GradDipCounsel (to Jul 04) A Eldridge RN R Eyers MA M Ferguson BA(Psych)(Hons) M Furlong BA(Hons) MCP J Garratt (to Apr 05) N Gillespie BA(Hons) S Gordon BEng(Hons) PhD M Grace RN M Grimmer BSc(Psych)(Hons) MSc(OccPsych) T Gunasekera BSc(Biotech)(Hons) B Haddon BA(Hons) (to Jul 04) N Hansell BSc(Hons) PhD A Hawkins BSc(Hons) PhD D Healey AssocDipSocSc D Hickey AssDipArts J Higgins BHlthSc A Hourigan BPsych (to Jan 05) F Husband M James BSc(Hons) MSc PhD S James CertInfoTech AssDipAppSc K Jordan BSc(Hons) M Keel (to Oct 04) L Kelpie RN K King BSc MSc Y Lafferty BA (Hons) (to Feb 05) C Laizans M Lee-Smith BAppSc(Psych) P Lind BSc(Hons) PhD M Luciano BPsych(Hons) PhD M Lynskey BSc(Hons) MSc PhD A MacKenzie BA C Madigan BNursing BHlthSc

101

Staff 2004–2005

D Magson E Mallon L Matthews K McAloney S McCoombe R McLaughlin S McMullen J McPhee B Morris L Nunn D Nyholt W O’Connell M Okello D Park H Park C Pink C Pretsel F Price I Putnoki J Quinlan C Redfern M Reilly D Reynolds J Rosa L Ryan L Saeck V Sellin S Shekar P Shertock D Smyth A Somerville K Sorensen D Statham V Stringer C Sullivan L Sullivan J Symmons H Taylor V Thomas J Tindale A Toivanen J Toohill S Treloar P Visscher A Wakefield L Walters-Hill K Watson C Wheat K White N Whiteman J Whitfield

GradCertHousingMgmt (to Oct 04) BA(Psych)(Hons) BCommerce BA(Hons) BA (to Aug 04) AssocDipCommunityRec GradDipPsych BPsych (to Jun 05) DipTeaching BSc PhD BA P/GDipEd P/ GDipSocPlan&Develop GradDipRehab BA BA(Hons) (to Dec 04) BA(Psych)(Hons)

BSc(Hons) BA GradDipHlthProm MHlthSc BLaw BSc(Hons) BEngineer BSc BA BA(Hons) MCP BA BSc (to Jul 04) BA BBus GradDipInternationalLaw BA RN BPsych(Hons) BNursing MMidwifery (to Nov 04) BSocSc MSc MsocWk PhD BSc MSc PhD (to Apr 05) BBus(HIM) AdvCertArts BA BSc(Hons) MSc PhD FRC Path FRACB

L Winkler J Wood M Wright BSc(Hons) PhD O Zheng G Zhu MPH BSc Hepatic Fibrosis G A Ramm BSc(Hons) PhD M Bertrand-Philippe MSc PhD T Pereira BSc(Hons) PhD L Ramm BSc R Ruddell BSc(Hons) PhD P Rutherford BSc (to Dec 04) C Xu BMed MMed PhD Iron Metabolism G J Anderson BSc(Hons) MSc PhD T Amos J Dixon RN BA(Hons) J Dodemaide BSc D Frazer BAppSc(Hons) PhD E Hay BSc(Hons) K Hyde K Millard BSc(Hons) T Murphy BSc MSc

102

M Pollard L W Powell

AC FTSE MBBS MD PhD D Univ(Griff) FRCP FRACP

D Raffelt V Shaw S Wilkins BSc(Hons) Melanoma Genomics P G Parsons BSc(Hons) PhD G Boyle BSc(Hons) PhD J Challacombe BAppSc (Hons) (to Apr 05) L Crowther BSc(Hons) K Ferguson J Johns BSc(Hons) A Martyn BSc(Hons) S Ogbourne BSc(Hons) PhD J Pedley BSc K Staib Cert LabSkills (to Dec 04) Molecular Epidemiology G Montgomery BAgrSc(Hons) PhD A Ali BAppSc L Bardsley BAppSc M Campbell BAppSc A Caracella BSc B Castellano BSc S Crooks BSc GradDip ClinMicrobiol C D’Amato BSc M Davey BAppSc (to Jun 05) A Dowling BSc M Downey BSc(Hons) T Dumenil BAppSc A Henders BSc(Hons) A Higgins BSc L Le BSc(Hons) MSc R Magson BSc (to Apr 05) L McNeill GradDipGeneticCouns BBiomedSc R Mayne BSc J Mountford BSc(Hons) J Palmer BSc BBiochem(Hons) S Thomas BSc S Thompson BSc Z Zhao MDentSc PhD THERAPEUTIC DEVELOPMENT AND CLINICAL RESEARCH DIVISION: Division Chair: DJ Moss Director: A W Boyd BMedSc(Hons) MBBS PhD FRACP University of Queensland Manager Therapeutic Development A McLean BAppSc(Biotech)(Hons) Manager Quality Assurance A Maksoud ADCLT BAppSc (to Oct 04) J Condren BSc (from Oct 04) Development Scientists M Bleasdale BSc(Hons) N Bleasdale BTechMngmt T Bodetti BAppSc(Hons) PhD K Bouyer BAppSc B Butcher S Chilcott BSc GradDipFood DrugAnalysis J Crowley RN M Lin MSc L Liu BMed MSc J McLean BSc (to Jun 05) S Parimi MBiotech D Pickering BAppSc S Sekuloski BSc(Hons) PhD M Twist AssocDipAppSc Administrative Support M O’Hara N Quirk Translation Research G Beadle MBBS FRACP FRACR T Jones BSc(Hons) K Kennedy BPsych(Hons) D Spooner BSocialSc(Hons) (to May 05) S Stein BAppSc

INDIGENOUS HEALTH RESEARCH PROGRAM Coordinator J Stirling DipTeach MPrimHlthCare V Clements BAppSc J Gaffney RN V Harrhy BSc S Shibasaki BAppSc MAppEpi (to Oct 04) COOPERATIVE RESEARCH CENTRE FOR VACCINE TECHNOLOGY Director A Kelso BSc(Hons) PhD Executive Officer/Assistant Director S Johnston BBus MSc Finance Officer L Leong BComm Communication Officer Jann O’Keefe Executive Secretary M Quince DipBus AUSTRALIAN CENTRE FOR INTERNATIONAL AND TROPICAL HEALTH AND NUTRITION (JOINT WITH THE UNIVERSITY OF QUEENSLAND) Director B H Kay BSc(Hons) PhD Executive Assistant P Fraley CORPORATE DIVISION Secretary and Chief Operating Officer M J Staley MSc GMQ MBA FAIM MAICD Assistant Secretary N Fox Executive Secretary to Sec/COO B Wanrooy Administrative Support C Green D Gunn S Hunting (to Apr 05) T Laing BA E Laszlo (to Jun 05) R Meaclem M Paul Finance Chief Financial Officer M Cornell BBus Accountant C Baldwin BEcon Assistant Accountant C McNally Grants Officers L Casey BSc GDTh F Khaya BA MAPublicPolicy Payroll Officer M Weaver AdvDipBus(Acct) Assistant Payroll Officer P Donnelly Accounts K Moran L Sanderson DipAppSc M Stromberg Human Resources HR Executive N Green BBus(HRM) MBA HR Officer L Lane HR Assistant M Anderson CertBus

Queensland Institute of Medical Research

Business Development Executive T Mynott BAgrSc PhD Assistant R Osborne Regulatory Affairs Executive A Mitchell BSc(Hons) PhD Administrative Officers J Chow BA BSc MPH N Fielding Cert Workplace Training DipAppSc BSc(Hons) Scientific Services Manager JA Cooper BSc MSc PhD GCertMgt Sequencing and Synthesis M Edmundson BSc MSc P Collins BSc(Hons) Flow Cytometry G Chojnowski BappSc P Hall BSc Histotechnology SH Park DipClinPath Animal Services S Cassidy CLabAnCare N Felder C Groennou C Kerwick BVSc M.A.C.V.S (Animal Welfare) R Lee BBus M McInnes CertAnimalCare E Skevos M Vandeleur S Whittam CLabAnTech Media L Jones Glassware G Cuthbert BNurs CSterTech V Matthews L Thompson (to May 05) S Watkins Store S Wood CWarehousing M Eaton A Girle T Kent M McDade Building and Security Manager A Stockman HND (Elec Eng) HTC (Plant) Workshop M Bugden TradeCert(Refrig) J-P Fahrner CKennel/CatPrac A McKee AssocDipElectEngineer G Madders ElectricMechanic/Fitter D Patrick AssocDipElecEngineer R Tyrrell EngFitter Security B Meyers Safety Safety Manager H Leonard BSc MSc PhD Safety Officers G Lawrence MBBS FRACP MD FAFPHM T Murphy BSc MSc

Queensland Institute of Medical Research

Information Technology Chief Information Technology Officer C Ward ADAB GradDip CommComp MACS Computing Services M Feodoroff BInfo D James S Jaremczuk BBiolSc MCP CAN D Johnstone DipInfoTech P Kaim BAppSc X Lin BEng Meng PhD S McDonagh BSc (to Aug 04) A Nutley-Govaerts BAppSc L Ward BInfoTech Graphic Support H Matthews BA CertPhotography I Anderson BInfoTech(Hons) S Sculley Library Services J Ho Development and Marketing: Director M Lagana BBus(PR) AssocDipSocSc General Manager C Borthwick BBusComm RN Office Manager M Elliott Bequests Officer M Gray RN Community Liaison Officer S Millman DipMktg BBusMktg Communications Coordinator L Moran-O’Connor (to Feb 05) Administrative Officers T Reddacliff E Waites VISITING SCIENTISTS Infectious Diseases and Immunology Division P Bartley BMedSc MBBS N Cloonan BSc (Hons) J Fawcett BMedSc(Hons) MBBS(Hons) PhD (to Nov 04) M Gatton BSc(Hons) PhD M Hernandez-Valladares (to Dec 04) C Hirunpetcharat PhD (to Jul 04) J Hou BMed (to Dec 04) L Hugo BSc(Hons) PhD C Hyland BSc MSc PhD K Klotz BAppScBiol MAppSc PhD (to Jul 04) A Khromykh BSc PhD T Le MSc BVSc(Hons) (to Dec 04) A Lenarczyk BSc(Hons) PhD Y Liu BA (to Oct 04) J Mackenzie BSc(Hons) PhD FASM FACTM A Mai (to Oct 04) L Mateo BSc MSc S Morroll BSc(Hons) PhD (to Feb 05) T Ngo M Pender MBBS FRACP PhD MD S Simsek DVM PhD T Skinner-Adams BSc(Hons) PhD T Spielmann MSc PhD M Steinitz PhD (to Sep 04) J Thompson BSc PhD (to Feb 05) G Williams BSc(Hons) MSc PhD J Wilks GradDipLegalPractice LLB(Hons) PhD BA(Hons) M Woods MD MPH H You (to Jan 05) Z Zhang (to Dec 04)

Cancer and Cell Biology Division M Bryant MBBs M Burger BSc(Hons) R Buttenshaw CertChem R Clark BSc(Hons) C Clarke BA(Hons) PhD A Cook BSc(Hons) M Cummings MBBS FRCPA PhD FIAC C Filippich BAppSc I Filippovich DipSc MSc DSc (to Dec 04) J Fleming PhD F Gardiner MBBS FRCS FRACS MD D Gotley MBBS FRACS MD PhD H Handoko BSc MSc PhD A Jones BSc MResBiotech S Lakhani BSc(Hons) MBBS MRCP MD FRCP J Larsen BSc(Hons) A Londono-Valejo MBBS PhD P Masci BSc MBiochem N Matigan BSc(Hons) B Mowry MBBS BA(Hons) FRANZP MD H Nguyen MD (to Apr 05) S Parry BSc(Hons) MSc S Prato BSc(Hons) (to Mar 05) V Rosenkov MD (to Feb 05) L Sauer BSc (to Jul 04) P Simpson BSc PhD H Smith BSc A Sofronis BSc(Hons) MSc N Sorokina DipBiochem DSc (to Dec 04) F Tomlinson MDFRACSPhDMBBS(Hons) CH Vo D Walker BMedSc MBBS(Hons) PhD T Yeadon Y Zheng (to May 05) Population Studies and Human Genetics Division K Andreasyan BDS MDS MPH J Aylward BSc MSc PhD C Bain BSc MBBS MPH MS Z Clavarino BA(Hons) PhD D Crawford MBBS MD FRACP (to Dec 04) P Hall MBBS FRCPA FC A Heath BA PhD L Kelly MBBS FRACR P Lewindon MBBS MRCP FRACP P Li BSc (to Apr 05) S Luong MD (to Nov 04) G MacDonald MBBS FRACP P Madden BS MS PhD C Nagle E Nelson BA MD S Nighswander-Rempel BSc J Smith BSc PhD R Sturm BSc(Hons) PhD R Todd BA PhD J Van der Pols BSc MSc DipScComm PhD A Wang BSc (to Dec 04) P Welburn J Wicks BEcon BSc(Hons) MA Therapeutic Development & Clinical Research C Nguyen BSc PhD (to Dec 04)

103

Research Students at QIMR – as at 30 June 2005

PhD Scholars: Y Adams C Anderson V Anderson B Andrew S Apte J Balen L Beattie T Bell B Benyamin T Bladen R Bowman J Brown A Burgess D Chin T Chuah W Chung J Condon B Cornes M Coulthard W Coventry B Datu M Davies M Dixon T Don R Dunne S Earl M Ellis J Evans M Ferreira M Georgousakis A Glanfield A Guerney E Hacker L Hall M Hamilton J Hancock J Hansen P Hawthorne E Holliday H Inglis J Jeffrey C Jekimovs M Jones J Jonnalagadda S Jordan

J Kelly T Knox S Kopp R Laherty M Lai K Landers E Lau A Lewis H Lin K Loh F Lose L Major T Maxwell A McRae S Medland M Merritt L Micallef R Middleberg S Mijajlovic J Miles L Moertel

104

BSc(Hons) BSc(Hons) MSc BSc(Hons) BSocSc(Hons) BSc(Hons) BSc(Hons) BAppSc(Hons) BSc(Hons) BSc(Hons) MAgriculture BAppSc(Hons) MBBS FRACP BAppSc(Hons) MSc(Hons) MBBCh FRCSI BMedSc MBBS BSc(Hons) BSc(Hons) BA BSc(Hons) MBBS FRACP FJFICM BAgrEcon GradDipSocSc BA(Hons)(Psych) BSc MPH BAppSc(Hons) BSc(Hons) BSc(Hons) BSc(Hons) BBiotech(Hons) BSc(Hons) MSc BSc(Hons) MBBS(Hons) BSc(Hons) BSc(Hons) BSc(Hons) BSc MEnt BSc(Hons) BTechBiomedSc(Hons) MBChB MRCP MRCGP BAppSc(Hons) BSc/BBusMgt BSc(Hons) BSc(Hons) BSc(Hons) BSc(Hons) BSc(Hons) BAppSc(Hons) BSc(Hons) BSc MSc MBBS(Hons) FRACGP DRANCOG GradDip Epidem BSc(Hons) BSc(Hons) BVetSc MBBS BSc(Hons) BAppSc(Hons) BSc(Hons) BSc(Hons) MBiotech MPhysio BAppSc MBiotech BSc(Hons) BAppSc (Hons) BAppSc(Hons) BSc(Hons) BA(Hons)(Psych) BSc(Hons) BSc(Hons) BSc(Hons) BSc GradDipIT BSc(Hons) BBiomedSc(Hons)

QIMR Supervisor J McCarthy N Martin M Good N Martin A Kelso D McManus M Good A Green N Martin H Leonard P Parsons M Lavin T Sculley P Parsons M Lavin D Kemp N Martin N Martin A Boyd N Martin A Loukas K Sriprakash D Gardiner A Loukas P Upcroft M Lavin D McManus A Green N Martin K Sriprakash D McManus B Kay N Hayward A Green C Schmidt M Lavin N Martin D Gardiner N Martin G Anderson B Kay K Khanna K Khanna K Khanna A Green

K Khanna B Kay J McCarthy M Lavin Schmidt M Lavin A Boyd G Trench A Nicol B Leggett A Spurdle A Suhrbier J Lopez N Martin N Martin A Green P Parsons N Martin P Parsons S Burrows D McManus

PhD Scholars: K Morley M Neller T Newton L Packer J Pagan Y Panpisutachai L Papp R Prasad L Randall N Ranjit P Rattanasena M Reiter D Roberts J Ross T Russell S Sadeghi K Savage D Sivakumaran K Smith M Smout L St Pierre T Steele C Stylianou A Suraweera A Sykes M Ting A Twist M Wainwright C Willis J Wright K Wynn Y Yang MAppSc Scholar: K Taylor MD Scholar: E Morris MPH Scholar: C Olsen S Parekh MPhil Scholars: B Day K Kenney P McBride M Smith D. Turkiewicz Honours Scholars: MBBS Y Anderson R Brennan M Chai T Chetter P Deering G Eng J Fleming L Gaces T Higgins P Hilton S Mason K McSweeney T Nguyen V Oakes L O’Moore J Pincombe S Rossotti J Salvage-Jones R Sarai S Smith BAppSc Scholars: L Whop

BSc(Hons) BAppSc(Hons) BSc(Hons) BSc(Hons) BSc(Hons) BSc MSc BSc(Hons) BSc MSc BSc(Hons) BBiotech(Hons) MSc BSc(Hons) BSc(Hons) BAppSc(Hons) BSc(Hons) BSc(Hons) BBiomedSc(Hons) BSc(Hons) MBBS MBChB BSc(Hons) BAppSc(Hons) BSc(Hons) BSc(Hons) BSc(Hons) BAppSc(Hons) BSc(Hons) MCommNut BA(Hons)(Psych) BSc MSc BAppSc(Hons) BAppSc (Hons) BMed MMed

QIMR Supervisor N Martin C Schmidt P Parsons N Hayward K Khanna M Good K Khanna G Kay C Engwerda A Loukas A Suhrbier C Schmidt QRI P Upcroft B Kay A Green K Khanna D Harrich A Green A Loukas M Lavin G Anderson A Boyd M Lavin J McCarthy A Boyd A Green N Martin D Kemp J Upcroft R Khanna D McManus

BAppSc GradDipEd

P Valery

BMedSc MBBS(Hons) MRCP

G Hill

BSc PhD MD

A Green A Green

BSc(Hons) BSc(Hons) BMedSc MBBS BSc MBBS MBBS

A Boyd A Kelso A Green D Moss A Boyd

BSc BA BBioSc BSc BSc BA BAppSc BSc BSc BAppSc BSc BSc BAppSc BSc BSc BSc BPsych BSc BSc BBiomedSc BSc BSc

N Martin S Burrows D McManus N Martin M Lavin G Ramm A Lopez D McManus D McManus J McCarthy P Parsons C Engwerda G Trench K Khanna N Martin N Martin C Engwerda T Sculley J McCarthy J McCarthy A Green

Queensland Institute of Medical Research

Location

Queensland Institute of Medical Research 300 Herston Road Herston Qld 4006 Australia Postal Address Post Office Royal Brisbane Hospital Qld 4029 Australia P F

(+61) 7 3362 0222 (+61) 7 3362 0111

W www.qimr.edu.au E info@qimr.edu.au Donations Hotline 1800 993 000 Director Professor Michael Good Deputy Director Professor Adèle Green This report was produced by Jann O’Keefe Jennifer Ho Design and Desktop Publishing: Julia Holland and John Wade Vizibility Printing: Worldwide Online Printing Spring Hill Gems courtesy of Mr Stuart Bishop CEO, Hardy Brothers Jewellers Adelaide Street, Brisbane Gemstone graphics courtesy of Charles Barron and Kevin Goldwater at Clemenger, Brisbane