December 2015 edition 24
ihbi
Institute of Health and Biomedical Innovation
IN THIS ISSUE
ADVANCES Cell culturing pioneer’s insights to aid IHBI cancer activities Industry focus a key element in tissue regeneration research Investigating fussy eating in push to overcome obesity Studies aim to prevent and treat childhood burns Big picture approach to equity and wellbeing Executive Director’s report
IHBI Professor Greig de Zubicaray
State-of-the-art equipment at the Herston Imaging Research Facility (HIRF)
Brain imaging technology enhances insight of function, surgery and recovery Language impairment occurs frequently after brain damage and can have a devastating effect on a person’s quality of life. New insights into brain structure and function show some impairments are preventable and existing treatments can be improved, as IHBI Professor Greig de Zubicaray is finding out. Professor de Zubicaray has joined IHBI as Deputy Director in a joint position with QUT Faculty of Health as Assistant Dean (Research). He brings a wealth of knowledge about the neurobiology of language and memory, cognitive neuroscience, neuroimaging and psycholinguistics. His research focuses on investigating mechanisms in the brain responsible for language processing and how injuries due to tumours and stroke affect those mechanisms. PRIMARY BRAIN TUMOURS Incidence is increasing, with seven in every 100 000 Australians diagnosed with primary malignant brain tumour. Up to 1900 people expected to be diagnosed in Australia next year and 1385 of those expected to die. Prognosis depends on factors such as patient age, fitness and tumour grade. A third to half of all patients diagnosed with left hemisphere tumours is likely to experience some type of language impairment after surgery. TUMOUR RESECTION Removal by surgery of all or part of a tumour in an organ or other body structure. RESECTION MARGIN The margin of apparently non-tumerous tissue around a tumour that has been surgically removed. The margin aims to ensure no portion of malignant growth is missed, extending past the edges of the tumour and into the surrounding healthy tissue. BRAIN RE-ORGANISATION The brain has an ability to enhance and reorganise its function by forming new connections between cells. This ability is most obvious during learning in childhood and re-organisation continues throughout the lifespan, and in response to injury. Brain functions are not necessarily confined to certain fixed locations.
Tumours and stroke impact the brain and its function in different ways. Tumours are generally slow growing. Their slow growth allows the brain to reorganise its language and cognitive functions in regions away from the tumour. A stroke, on the other hand, is sudden and often without warning, and can directly affect language and cognitive functions.
“Different pathophysiological mechanisms responsible for stroke and primary brain tumours necessitate different approaches and imaging protocols,” Professor de Zubicaray says. “It is exciting to have access to state-of-the-art imaging equipment and leverage those capabilities to design projects that advance our understanding in these areas.”
It means Professor de Zubicaray’s research needs to consider both the treatment options for people with a tumour, ensuring surgery does not impact functioning areas of the brain, and for people who experience a stroke where language processing areas are damaged and recovery can vary.
Such knowledge has the potential to improve the survival rates and quality of life of people with brain tumours and those recovering from a stroke.
Language is very important in recovery, given its impairment is directly linked to a person’s ability to return to work, social interaction and even long-term survival. “The general aim of surgery is to remove as much tumour as possible while minimising the impact on language, motor and cognitive functions,” Professor de Zubicaray says. “Slow-growing tumours are often not associated with language impairments pre-operatively due to the brain’s ability to re-organise its networks. Surgeons need to account for the re-organisation of function when removing affected tissue, ensuring patients do not experience post-operative language impairment. In addition, knowledge about the type of brain damage caused by stroke can lead to better targeted treatments for language recovery.” Advancing Professor de Zubicaray’s research is state-of-theart biomedical imaging technology at the newly-constructed Herston Imaging Research Facility (HIRF).
HIRF involves IHBI partnering and collaborating with the Royal Brisbane and Women’s Hospital, the University of Queensland, and the QIMR Berghofer Medical Research Institute. The facility will enhance understanding of the human body and improve patient diagnoses and treatments via research and training activities. HIRF adjoins the hospital, providing access to patients and staff for clinical trials. The technology available at the facility will progress IHBI research into brain disorders, cardiovascular disease, injuries and cancer. Professor de Zubicaray is designing research projects that involve capabilities in neuroimaging with MRI. The technology will also enable him to expand his knowledge in how a person’s genome, a complete set of DNA that includes all genes, enables the human brain’s unique capacity for speech.
Cell culturing pioneer’s insights to aid IHBI cancer activities IHBI is working with a world-leading researcher in developing potential early and effective treatments for cancer patients. Teams working with Professor Jean-Paul Thiery aim to culture cancer cells from blood to tailor medicines for individual patients. Professor Rik Thompson
IHBI Professor Rik Thompson is at the centre of a collaboration with Professor Thiery that resulted in his visit to Australia to spend two weeks in IHBI laboratories and share his knowledge with researchers and students. Professor Thiery developed the most successful method yet for culturing small numbers of circulating tumour cells (CTCs), cancer cells present in blood that are responsible for metastasis. The culturing enables researchers to increase the cell numbers to a point of critical mass for testing medicines. IHBI researchers aim to use the method of harvesting and propagating cancer cells for treating with various cancer medicines in the laboratory, to test for efficacy before one day being prescribed to patients. Professor Thompson says not all medicines benefit all cancers – or patients. Testing medicines in laboratories using the cultured CTCs can be completed in as little as four weeks and could eventually save patients from receiving a cocktail of ineffective drugs, he says. “The challenge is that metastasis is often a killer and can be very different cancers from the original primary tumour,” Professor Thompson says. “It is difficult to identify every metastasis deposit in the body, but we think the most aggressive cancer deposits will be represented in the blood and therefore picked up in Professor Thiery’s culturing method.
CTCs are cells that have shed from a tumour deposit and circulate in the bloodstream. They constitute seeds for subsequent growth of additional tumours, called metastasis, in vital distant organs. Metastasis is responsible for the majority of cancer-related deaths.
characteristics and rules out a “one size fits all” approach. Using cultured CTCs for screening medicines is a major step towards a future in personalised medicine, involving the tailoring of medical treatment to the individual needs of each patient.
Metastatic tumour has cells that derive from the original tumour. That means, for example, that if breast cancer metastasises to the lungs the secondary tumour is made up of abnormal breast cells – not of abnormal lung cells. The tumour in the lung is then called metastatic breast cancer, not lung cancer.
The culturing method has the potential to provide insights for IHBI lung cancer expert Professor Ken O’Byrne, Australian Prostate Cancer Research Centre – Queensland director Professor Colleen Nelson and head and neck cancer researcher Associate Professor Chamindie Punyadeera.
Professor Thompson says the differences between cancer cell types and behaviours within – and between – patients means each treatment regime needs to take into account unique
Professor Thompson’s collaboration with Professor Thiery will involve sharing research data, jointly analysing results and writing papers for scientific journals.
PROFESSOR JEAN-PAUL THIERY Considered a pioneer in the field of epithelial mesenchymal plasticity (EMP), Professor Thiery has made seminal contributions in cell adhesion, cell migration, morphogenesis and cancer. He co-discovered an important mutation (FGFR3) in bladder carcinoma, now considered the best prognostic marker for superficial tumours. Professor Thiery also identified cell changes in breast carcinoma, ovarian carcinoma and uveal melanoma to define new prognostic indicators and therapeutic treatment. He is an emeritus scientist at Centre national de la recherche scientifique in Paris and visiting professor at the National University of Singapore. In 2009, Professor Thiery was made Chevalier in the Order of Légion d’Honneur (Knight of the Legion of Honour).
“It means we can harvest these cancerous cells and test medicines on them in a lab, before they are tested on patients. This will allow us to more quickly identify the most effective therapeutics for treatment.”
Industry focus a key element in tissue regeneration research Product development is an area of expertise increasingly sought for successfully translating innovations in health and medical research. The area is vital for researchers working closely with industry to commercialise medical devices, therapeutics and treatment programs. Felix Wunner
IHBI Professor Dietmar W Hutmacher has a track record of combining his research with industrial collaboration in advancing work in the fields of biomaterial science, tissue engineering and regenerative medicine. Large numbers of patients have been treated with CE-marked and Food and Drug Administration-approved bone engineering scaffolds developed by Professor Hutmacher’s research group. The scaffolds can be implanted into the body to encourage repair and regrowth where tissues are diseased or damaged. A patient’s stem cells can be added to encourage the correct WHY SHOULD RESEARCHERS COLLABORATE WITH INDUSTRY? Researchers need to understand how their innovations can be turned into products that people will use around the world. That includes understanding an industry’s machinery, manufacturing processes and staff capabilities. Innovations that can be turned into products without a major investment in new machinery or processes are more attractive to industry. A major investment also means the products are more expensive – and potentially out of reach of many people around the world. WHAT IS SCALE-UP? The ability to adjust processes so products created in small quantities in research environments such as laboratories can be manufactured in bulk to the same consistent standard by industry.
tissue to grown. In time, the scaffold will dissolve and be replaced by new tissue. Potential uses being investigated at IHBI include repairing broken bones, growing new breast tissue following a mastectomy and healing cartilage defects. Developing scaffolds that will effectively replace diseased or damaged tissue requires precision. PhD candidate Felix Wunner aims to improve the scaffold design and focus on the fabrication process using a melt electrospinning printing technique pioneered in Professor Hutmacher’s laboratory. Mr Wunner has joined IHBI from the Technische Universität München in Germany, bringing a background in mechanical engineering and a focus on product development. His studies at IHBI involve using a monitoring and control system in melt electrospinning, a process of drawing liquefied polymer materials under an electrostatic field to design the scaffolds. “I am developing a method that will enable enhanced control over scaffold fabrication using a melt electrospinning process,” Mr Wunner says. “I am designing a circuitry system for monitoring and regulating that will overcome instabilities in melt electrospinning technology to ensure accuracy and reproducibility in the future. “It means we can design scaffolds with microscopic precision. That is important because we need even dimensions and control over the outcome. Every scaffold produced needs to conform so
Prevention
Intervention
Translation
|
Prevention
Intervention
Translation
that we secure approval from international regulatory bodies when bringing the technology from the lab bench to the bedside.” The aim is to one day have 3D printers in hospital surgical suites producing the scaffolds on demand. Damaged or diseased tissues could be scanned on entry and a patientspecific scaffold created on the spot for implanting. Mr Wunner says realising that goal takes innovation that industry can easily adopt to incorporate into its production processes, without the need for investing in expensive new equipment and major staff training. But before the innovation reaches that point, it requires input from researchers with wide-ranging expertise, including cell biology, surgical processes, material science, computer modelling and systems engineering. “IHBI has that multidisciplinary environment – people coming together and having their input,” Mr Wunner says. “Everybody wants to use the fabrication method and the devices for different purposes. Understanding all their demands and integrating the complex requirements is challenging but it keeps the work interesting.” Support for the research stretches beyond IHBI to include QUT’s Electrical Engineering Workshop, especially electricians Brendon Stichbury, Graham Wright and Les King.
|
Prevention
Intervention
Translation
|
|
Investigating fussy eating in push to overcome obesity
Holly Harris
Eating nourishing food such as fruit and vegetables from an early age is essential for long-term health and prevention of chronic diseases. Fussy eating in childhood is a predictor of a poor diet in early adulthood. IHBI PhD candidate Holly Harris is using a collaboration with the University College of London to provide new insights into fussy eating.
WHAT IS FUSSY EATING? Refusing to try a new food at least half of the time. Do: Be a good role model; create a routine; stay calm; encourage self-feeding; remember children will not voluntarily starve themselves; and seek help from a doctor, if needed. Don’t: Delay introducing lumpy food; threaten, nag or yell; make a fuss; or use sweet treats as bribes. PROFESSOR JANE WARDLE Professor Wardle was Professor of Clinical Psychology and Director of the Cancer Research UK Health Behaviour Research Centre at the University College of London. She was a pioneer in health psychology and known internationally for her work on the contribution of psychology to public health. Professor Wardle died in October. She will be remembered for work on the role of psychological research in cancer prevention and the behavioural and genetic determinants of eating behaviour and obesity.
Fussy eating is an issue for between 14 and 50 per cent of toddlers and preschool aged children, with the wide range of prevalence partly blamed on parental interpretation of perceived food refusal and fussy eating. As well as resulting in a poor diet, fussy eating often causes parental anxiety, frustration and conflict. Ms Harris aims to understand the psychosocial and environmental factors linked to fussy eating. She will work with families to examine the roles of feeding patterns, parental perceptions of fussy eating, a child’s temperament and intake of nourishing food. Working under the supervision of IHBI professors Lynne Daniels and Karen Thorpe, she will also analyse previous studies, including a UK study that used a large cohort of twins. Her aim is to develop intervention tools to support parents in providing the best environment for healthy eating and overcoming food rejection behaviour. The ultimate aim us to add to the momentum to reduce global obesity rates.
behaviours? A major issue is parental understanding of what fussy eating is – and isn’t – and what it means. Once they understand that, parents can most effectively respond.” Social, cultural and economic factors also influence how parents feed their children and respond to fussy eating. “Socioeconomic disadvantage, that is low levels of education or income, does appear to play a role,” Ms Harris says. “So do ethnicity, the weight and general health of parents, feeding knowledge, beliefs, attitudes and practices.” Ms Harris received a boost to her studies, with an Endeavour Postgraduate Scholarship to enable six months of research in the UK, working with Professor Jane Wardle and gaining an insight into her research on child eating behaviours and energy balance. “Professor Wardle was a wonderful mentor,” Ms Harris says. “She was a brilliant researcher, a gifted leader of an amazing research team and charismatic woman.”
Fussy eating is linked to poor diet into adulthood, particularly a preference for energy-dense but unhealthy food rather than nourishing options. Studies show fussy eaters often do not consume enough fruit and vegetables.
The time at the University College of London assisted Ms Harris in designing her research program and refine research and networking skills. She wrote a manuscript of her findings, being reviewed for publication, and plans to present at three conferences.
It is a difficult area for researchers, given the factors that can play a role in a child’s fussy eating. For example, refusing familiar food may be a sign a child is full rather than fussy. Mealtime structure may also play a role.
“The Endeavour scholarship has given me a platform to broaden my research networks on a global level,” Ms Harris says. “It has given me the edge to make a significant contribution to research.”
“Familiarity of food and eating patterns is a key in avoiding difficulties,” Ms Harris says. “But what if there are difficult
Ms Harris also received a scholarship to attend the World Obesity Federation’s Scope School London 2015.
Dr Leila Cuttle
Studies aim to prevent and treat childhood burns Burns from hot water and hot objects is common among children, often causing pain, scarring and long healing times. Gaps remain in the knowledge about factors determining whether a burn is superficial or deep. IHBI’s Dr Leila Cuttle aims to fill in the gap to assist with prevention and treatment strategies.
WHAT IS THE DIFFERENCE BETWEEN A BURN AND A SCALD? A burn is caused by dry heat, such as an iron or fire. A scald is caused by something wet, such as hot water or steam. WHY DOES IT TAKE SEVERAL DAYS TO PREDICT SCALD BURN DEPTH? Scalded tissue can continue to self-destruct in the days after the wound has occurred, leading to deeper wounds. HOW DOES A CHILD’S PROGNOSIS DIFFER BETWEEN SUPERFICIAL AND DEEP BURNS? Superficial burns will generally heal within two weeks without scarring. Deep dermal burns will heal with a scar and many require grafting and repeated reconstruction operations.
Much of what is known about burns, healing and scarring dates from studies conducted in the 1940s. But advances in histology, the study of the microscopic anatomy of cells and tissues, enables researchers to gain greater insights.
conducts biological studies using burn wound models and combines that with her team’s expertise in cell and molecular biology, proteomics – the large-scale study of proteins in living cells, tissue pathology and mathematical modelling.
Dr Cuttle aims to use histology to understand the relationship between temperature, duration of heat exposure and depth of burn. The understanding will assist in diagnosis and treatment, given scald injuries are less predictable or uniform than contact burns and it can take doctors several days to distinguish areas of different burn depth.
Her work also aims to determine the temperature at specific skin depths at which tissue becomes injured, for insights into an equally important facet of health and wellbeing: prevention. The research conducted in the 1940s is still used to determine, for example, the safe temperature for bathroom hot water taps.
Understanding burn depth is important for gaining an accurate picture of tissue destruction, the potential need for grafting or other reconstruction, likely injury progression, healing and scarring. “Superficial burns will generally heal within two weeks without scarring,” Dr Cuttle says. “Deep dermal burns will heal with a scar and many require grafting and repeated reconstruction operations throughout childhood. “We need the best possible information so doctors treating children can assess the extent of burn tissue destruction as early as possible. That will help with understanding the progression of the injury and predicting healing outcomes for children.” Dr Cuttle’s research involves analysing protein composition in burn tissue at different skin depths as it heals in time. She
Prevention
Intervention
Translation
|
Prevention
Intervention
Translation
|
Collaborations have been established between IHBI researchers, including Dr Cuttle, based at the new Centre for Children’s Health Research and doctors at the adjoining Lady Cilento Children’s Hospital. Dr Cuttle says the collaboration provides an opportunity to impact on the 2000 children hospitalised in Australia each year for burns and scalding. “We have scientists and clinicians working together,” she says. “We have access to patients and their samples and that enables us to do some good analysis on skin, wound healing and scarring that will enable better outcomes for children with burn injuries. “I am working to ultimately improve and perfect skin wound healing, especially by improving acute treatment within 24 hours of the burn. That includes promoting first aid and its benefits to healing, minimising pain and understanding healing as part of the best possible treatment strategies.”
Prevention
Intervention
Translation
Professor Greg Marston
Big picture approach to equity and wellbeing Among the most serious problems threatening people’s wellbeing are poverty and climate change. IHBI Professor Greg Marston is leading a research project that takes a big-picture approach to addressing the problems, involving scientists, policy makers, urban planners, environmentalists and community members.
SOCIAL DETERMINANTS OF HEALTH Defined by the World Health Organisation as the conditions in which we are born, grow up, live, work and age, shaped by the distribution of money, power and resources at global, national and local levels. Factors include income and employment status; access to education, healthcare, affordable housing and transport; stress; age; and disability. POVERTY Limits the ability to buy healthy foods such as fresh fruit and vegetables. Associated with increased risk of diseases such as heart disease and some cancers. Also associated with increased rates of smoking, alcohol consumption and drug dependence. ENVIRONMENTAL RISK FACTORS Play a role in more than 80 major diseases and injuries around the world.
It takes a global outlook to understand the issues and input from people with a wide range of expertise. The newly-funded collaboration has input from experts from Lund University, QUT and The University of Queensland. Professor Marston says the aim is to bring people from the Australian community, scientists and decision-makers together and work to move to a low-carbon economy – and in the process, ensure a greater level of inequity does not develop. A transition to a low-carbon economy in Australia may also set an example for developing countries to follow, he says. “Without making changes, inequity is likely to be exacerbated,” Professor Marston says. “In first-world countries including Australia, traditional social support networks such as public health, public housing and income assistance face increasing government funding competition from prioritised environmental policies such as flood and drought management.”
It is understood that inequality is a significant factor in individual and collective ill-health and ill-being. Poor people are at greatest risk, with increasing food prices and incidence of natural disasters due to our changing climate among the most evident challenges. Professor Marston says developed countries are not immune from inequity. “There is ample evidence that increasing consumption adds little to social wellbeing and human happiness – and can actually impede societal wellbeing if social inequities become too great.” His collaborative research project will look at what can be learned from other countries about creating better links between social policy and urban planning that encourages transit-oriented developments with low carbon emissions. Such developments have the potential to provide affordable housing, increase public transport use and reduce carbon pollution – but only if people want to live in them. “People need to be involved in the research project and their input given significant weight, alongside that of scientists, policy makers and urban planners.
Equity is also becoming an increasing issue in developing countries. India and China have the greatest absolute numbers of the global poor. The two countries have moved from low to middle-income status in the past 10–20 years. Yet poverty in global aggregate numbers has not fallen significantly, meaning that most of the world’s poor people now live in middle-income countries.
“They need accept the developments as a means of encouraging low-carbon behaviour change. We can make policy changes and encourage urban planning, but it comes down to people accepting and embracing what we provide. They have to see the developments as a way of improving their lives, especially their health and wellbeing.”
Health and medical researchers are specialists, with extensive knowledge in their selected field and a deep understanding of context, often related to genetic, behavioural or environmental factors involved in disease and injury. They work in collaboration with researchers in other disciplines because health issues are complex.
Collaboration is also expected to result from neuroscientist Professor Greig de Zubicaray’s use of equipment at the newlyconstructed Herston Imaging Research Facility. The facility is bringing together experts from research institutes and health services and promises to progress IHBI research into brain disorders, cardiovascular disease, injuries and cancer.
long-term ill-health and chronic diseases. She will work with families to examine how feeding patterns, parental perceptions of fussy eating and a child’s temperament can make a difference in ensuring an intake of nourishing food.
Working at IHBI provides researchers the opportunity to build those networks and share knowledge. This edition of IHBI Advances shows the diversity of research conducted at the institute and the varied methods employed to progress work from the laboratory to hospitals and clinics.
Another new facility established with collaboration and clinical application in mind is the Centre for Children’s Health Research. Dr Leila Cuttle expects the CCHR’s proximity to the Lady Cilento Children’s Hospital will prove beneficial in her research into the diagnosis and treatment of children’s burns.
Few research facilities cover as many areas of strength and innovation, as detailed in these pages: cancer, neuroimaging, children’s burns, biofabrication, nutrition and the links between wellbeing and environmental policy-making.
An important element in the translation of research into clinical outcomes and the wellbeing of people around the world is working with decision-makers to ensure a suitable policy framework and environment. Professor Greg Marston is working with an expert from Lund University in Sweden to understand links between inequity, poverty, support networks and social policy.
Diarrhea, lower respiratory infections, various forms of unintentional injuries and malaria are largely the result of environmental risk factors and most affect the poor in developing countries. As the climate changes, health impacts are expected to worsen, particularly for the poor.
EXECUTIVE DIRECTOR’S REPORT
Another $34 000 was also awarded as part of a Discovery International Award to fund Professor Max Koch from Lund University in Sweden to visit Australia to collaborate with the research team and policy-makers on developments in Europe.
IHBI Professor Rik Thompson is a fine example of a researcher collaborating globally to develop new treatments for cancer patients. Cancer is a particular area of IHBI research strength. Professor Thompson’s collaboration with Professor Jean-Paul Thiery has the potential to advance IHBI activities in breast, lung, prostate and head and neck cancer.
There is also an international flavour to research in the laboratory of IHBI Professor Dietmar W Hutmacher. PhD candidate Felix Wunner has joined the laboratory from the Technische Universität München in Germany, bringing a background in mechanical engineering and a focus on product development. He aims to improve the design and fabrication of implants that encourage repair and regrowth where a person’s tissues are diseased or damaged. It is pleasing to see international collaboration, innovation and insight coming together to create an environment in which prevention strategies and treatments of complex health issues are being developed and translated into better health services and equipment. This is the final edition of IHBI Advances for 2015. I wish you a safe and healthy holiday season.
Work at the University College of London earlier this year enabled PhD candidate Holly Harris to gain a better understanding of fussy eating and its impact on potential
Professor Lyn Griffiths Executive Director, IHBI
ihbi
FIND OUT MORE: support IHBI Yes, I would like to support IHBI’s health research If you would like to help us make the possibility of better health a reality, please fill out the form and send it with your donation to: QUT Alumni and Development Office GPO Box 2434 Brisbane QLD 4001 Australia
Institute of Health and Biomedical Innovation
I would like to receive updates about IHBI’s research
post
Name Address
Postcode
Email address Yes, I would like to donate to IHBI’s work
Phone +61 7 3138 7162 Email supportihbi@qut.edu.au | Contact Senior Development Officer
Please debit my credit card:
Visa
My cheque of $____________ is enclosed
MasterCard
Amex
Expiry:
/
/
Donations of $2 and over are tax deductible I am interested in making a monthly donation via eftpos or credit card. Please send me further information. A secure electronic donation service is also available. Please visit www.giving.qut.edu.au to contribute. Please send me information on how I can include IHBI in my will.
© QUT 2015 21855
Professor Marston is leading a collaboration that aims to understand inequity and the links between wellbeing and environmental degradation. The collaboration has secured $210 000 in funding from the Australian Research Council to determine the roles of planning and social policy in lowering carbon emissions.