Australian Life Scientist Jul/Aug 2014 by Westwick-Farrow Media

Biomarkers PP100009448 ISSN 1448-9791

Harnessing Fc receptors

Vol 11 Issue 4 • July/August 2014

AMBASSADOR FOR SCIENCE | MEDICAL DEVICES | CLINICAL BIOCHEMISTRY

Contents FACE TO FACE

12 Ambassador for science A passionate advocate for science, Professor Lyn Beazley shares some of the exceptional and continuing contributions she has made to Australian science over a career that began with an affinity for biology.

AUSBIOTECH

BIOMARKERS

CONFERENCE PREVIEW

16 Call for tax reform

18 Monoclonal antibodies and immunomodulation

32 Clinical biochemistry

Industry is calling for further tax reform as the annual Biotechnology Industry Position Survey has revealed that Australian advanced manufacturing companies are increasingly heading overseas.

Professor Mark Hogarth has spent most of his career studying the role of Fc receptors in inflammatory and auto-immune disorders. Found on the surface of a variety of immune cells, these antibody-binding receptors are now prospective targets for new treatments of inflammation. They are also involved with therapeutic monoclonal antibodies in cancer and manipulation of vaccines in HIV-AIDS. MEDICAL DEVICES

22 Bespoke biotech

Personalised, predictive, preventive, and participatory - the Australasian Association of Clinical Biochemists will hold their Annual Scientific Conference in Adelaide in October.

Additive manufacturing and 3D printing technology have a lot to offer makers of biomedical devices.

12 REGULARS

06 10 26 33 34

Movers and shakers GrantWatch New products Publish or perish Events

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The medical bioeconomy The recent Federal Budget announcements were a mixed bag for the life sciences. Significant cutbacks in some areas and exciting positives for medical research, particularly in the form of the proposal for a $20 billion Medical Research Future Fund (MRFF). This is an early indication that while there will be ongoing support from the Abbott government for research, the structures and oversight will be different from anything previously experienced. While the government is still forming its views on the how the fund will operate is the time for the research community to contribute to the thinking. In the case of the MRFF, it will operate under the watchful eye of a governance approach more akin to investment banking. After all, it has been created by the rolling over of the existing $1 billion of ‘uncommitted funds’ from the Health and Hospitals Fund managed by the Future Fund Board. What will be crucial is the range of activities that can be supported under the umbrella of the proposed MMRF. The devil will be in the details yet to be announced. It would be a great outcome for investment principles if the MRFF could financially support all the components that make up a medical research outcome. Well placed to comment on these matters and leading the debate currently is Simon McKeon, executive chairman of the Macquarie Group. His chairing of the 2012-2013 Review of Health and Medical Research in Australia, his chairmanship of CSIRO and his comments to the National Press Club in Canberra in June of this year has provided insights and guidance for the government to consider. McKeon’s focus at the Press Club was on “health economics”, “integrated health

research clusters”, “investment returns”, “KPIs relating to research outcomes”, “facilitating trials by streamlining the number and scope of ethics committees nationally”, and advocating a “massive increase in the number of practitioner fellowships”. All sound, but what is critical at this juncture is that the enabling legislation and funding guidelines established for the MRFF provide for the range of activities along the innovation system - support infrastructure, scaled research funding, clinical trials, early-stage finance, facilities for technically advanced manufacturing and soon. It will be to our shame to simply ‘pump-prime’ the research community and not achieve the purpose of the public investment - firstly, the growth of a whole industry sector - the ‘medical bioeconomy’, and secondly, improved health outcomes for Australians. When we work with scale, a sense of national purpose and the eye of an investment banker, science can achieve our national potential - that has been a central part of Australia’s economic success over the past century. To keep that success going means reforming the innovation system so it all works. Centralisation, collaboration and integration around the latest technology and changes to our regulatory frameworks are key. The establishment and workings of the MRFF will be an important debate to get right and one we need to be active in supporting because it will have significant knock-on consequences for the conduct of all scientific research in Australia. Dr Steve Winslade (guest editorial) CEO, Australian Phenomics Facility The Australian National University, Canberra

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MOVERS & SHAKERS

New head for Academy of Science Professor Andrew Holmes has formally taken over as president of the Australian Academy of Science, becoming the 18th president of the academy. Professor Holmes succeeds Professor Suzanne Cory, who has been in the position since 2010. The presidency alternates between the physical and biological sciences every four years. Currently a Photo credit: Australian Academy of Science Melbourne Laureate Professor Emeritus at the Bio21 Institute in the University of Melbourne and a CSIRO Fellow at CSIRO Materials Science and Engineering, Professor Holmes has been recognised for his groundbreaking work on light-emitting polymers. These polymers play an important role in the newly emerging field of flexible electronics and have applications in flatscreen televisions and solar cells. Professor Holmes was elected to the academy in 2006 and has served as foreign secretary since 2010. He is also a Fellow of the Royal Society of London and a Fellow of the Australian Academy of Technological Sciences and Engineering. Along with a new president, two new secretaries of the academy have taken office - botanist Professor Pauline Ladiges has taken over from Professor Jenny Graves as secretary of education and public awareness and mathematician Professor Cheryl Praeger has taken up the role of foreign secretary.

GM farmer wins court case The Western Australian Supreme Court has dismissed organic farmer Steve Marsh’s claims for damages over contamination from his neighbour Michael Baxter’s genetically modified canola crop. Mr Marsh claimed the contamination caused him to lose his organic certification on more than half his Kojonup property for almost three years. Mr Baxter is a conventional farmer growing crops that include genetically modified or Roundup Ready canola. The trial found that there was no evidence of genetic transference risks to neighbouring property by the Roundup Ready canola, noting that the Marshes had never grown canola on their property. The decision gives farmers - organic, conventional and GM crop farmers - assurance that they can co-exist, even when their production systems differ. As Dr Andrew Jacobs from the Australian Centre for Plant Functional Genomics noted, the case reflects poorly on Australia’s organic certification body, the National Association for Sustainable Agriculture (NASAA), which has zero tolerance for contamination in broad acre crops. Similar accreditation bodies overseas allow for small amounts of unintended presence of other seeds. “We hope that the NASAA policy might be reviewed and brought in line with similar policies around the globe to support farmers wishing to grow crops for their niche markets. GM crops can be consistent with organic farming,” said Dr Jacobs. AusBiotech also welcomed the decision, stating that it “… reaffirms the importance of coexistence principles that allow farmers to benefit from continually evolving agricultural technologies that have been demonstrated scientifically to be safe and effective. Without access to technological developments, our agricultural industry will certainly fail to compete with international markets where these technologies are adopted.”

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Blood test for bowel cancer An Australian-developed DNA blood test for colorectal cancer (CRC) has a successful detection rate of 65% and could help overcome the barriers to screening associated with faecal tests. The test - developed by Clinical Genomics and CSIRO - has a detection rate that raises to 73% for cancers that are stage II or higher.

The DNA test screens for two genes, BCAT1 and IKZF, which are known to hypermethylate in CRC tumours. It was recently used to analyse blood specimens collected from more than 2000 Australian and Dutch volunteers scheduled for colonoscopy or for bowel surgery. Clinical validation was conducted with Flinders University’s Flinders Centre for Innovation in Cancer. The detection rate data were presented at the Digestive Diseases Week 2014 conference in Chicago by the centre’s Professor Graeme Young. Professor Young said based on data to date, the test could be a candidate for population screening. “If this test becomes available in the future I think the message would need to be that the faecal test is the best place to start for people who are due for screening. Then the plasma test would be for those people who can’t or won’t screen with a faecal test.” Clinical Genomics CEO Dr Larry LaPointe said the test could be available to Australians on a userpays basis as soon as early spring.

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MOVERS & SHAKERS

Public research organisations are driving advances in research into genome-related technologies, according to a new report from intellectual property firm Marks & Clerk. Presented at the BIO International Convention 2014 in San Diego, the Life Sciences Report shows that US public organisations dominated the list of the top filers of patents for personalised medicine-related inventions between 2003 and 2013. Overall, the gap between the number of patent applications filed by public and private organisations has increased since 2006, the report states. The US-based National Institutes of Health (NIH) was by far the biggest

Public sector drives personalised medicine

filer of applications in this time, with 304 patent families filed. But the private sector's Roche was second with 127. The US is also leading the pack in terms of the number of personalised

medicine patent applications per region, with 8382 applications filed between 2003 and 2011. This compares to 4383 for Europe, 2606 for Japan, 2359 for Canada and 2335 for Australia. During this period, over half of the top five patent applicants’ patent families related to cancer treatment. In contrast to personalised medicine, where innovation is driven by the public sector, private companies are leading patent applications in the field of sequencing technology. The largest share of applications again comes from the US, with 2871 filed since 2003. Europe and Japan also feature strongly with 739 and 520 publications respectively.

Insights into plant immunity

The world’s first international masters in biofabrication is being offered by the Queensland University of Technology (QUT), the University of Wollongong, the University Medical Center Utrecht in the Netherlands and the University of Würzburg in Germany. The four universities have joined forces to offer a two-year, twodegree masters program whereby graduates will hold a masters degree from an Australian university in addition to a masters degree from a European university. Biofabrication is a multidisciplinary area of research that required an understanding of chemistry, physics, biology, medicine, robotics and computer science. It involves the use of 3D printing to regrow and replace most types of human tissue. These tailor-made structures are implanted into the body to act as scaffolds on which new tissue can grow, and as the tissue grows the scaffold dissolves into the body. For example, biofabrication is successfully being used successfully to repair broken and missing bone. “Each of the four universities has established a track record in key areas of biofabrication, including polymer chemistry, cell biology and clinical implants,” said Professor Dietmar W Hutmacher, who leads QUT’s biofabrication research. “Biofabrication can be used to repair cartilage, bone, muscles, nerves and skin that have been damaged by trauma, disease or cancer. It is even predicted that entire organs will be biofabricated within a few decades.” Each of the four universities will admit 10 students to the degree. Australian students will spend nine to 12 months studying at one of the European universities and European students will also study at one of the Australian universities. The masters in biofabrication is supported by the Australian Government and the European Union.

Plants acquire broad spectrum disease protection from -aminobutyric acid (BABA), research has found. The collaborative research, led by researchers at the University of Sheffield in the UK and including scientists from the University of Western Australia, identified the enzyme, an aspartyl tRNA synthetase designated IBI1, as the key receptor that binds BABA. This class of enzymes play a key role in the primary metabolism of cells but had not previously been linked to immune responses in plants. The binding of BABA to the IBI1 receptor ‘primes’ the plant immune system. BABA has long been known for its protective effects against devastating plant diseases, such as potato blight, but has not been widely used in crop protection because of undesirable side effects - it suppresses plant growth when applied in high doses. The researchers found that BABA-activated IBI1 controls plant immunity and growth via separate pathways. “Since plant immunisation by BABA is long-lasting, primed crops would require fewer applications of fungicides, thereby increasing sustainability of crop protection. Furthermore, immune priming boosts so-called ‘multi-genic’ resistance in plants. Plant immunity that is controlled by a single resistance gene, on which most conventional breeding programs are based, is comparably easy to overcome by a pathogen. By contrast, priming of multi-genic immunity by BABA is difficult to break, thus offering more durable crop protection,” said the study leader Dr Jurriaan Ton. The research was conducted on the mustard plant, Arabidopsis thaliana; however, the researchers are confident the findings will be transferable to crop plants.

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MOVERS & SHAKERS

GrantWatch Qld Government supports MRCF The Queensland Government plans to inject $1 million into the Medical Research Commercialisation Fund (MRCF), a VC fund dedicated to supporting the commercialisation of early-stage medical research. The MRCF also receives funding from the federal government and the governments of Victoria, New South Wales and Western Australia. So far the MRCF has invested in 12 companies, including two medical technology startups based on research from the University of Queensland’s (UQ) Centre for Clinical Research and its Australian Institute for Bioengineering and Nanotechnology. The two start-ups are Q-Sera and Vaxxas. Q-Sera is commercialising technology for producing high-quality serum for analysis in a clinical setting. Vaxxas is commercialising Nanopatch, a pain-free method of vaccine delivery designed to replace needles and syringes. Both start-ups were established with the support of UQ’s main commercialisation company UniQuest. UQ Deputy Vice Chancellor for Research Professor Anton Middelberg welcomed the funding commitment from the Queensland Government. “Since the global financial crisis, there have been very few new venture-backed companies in Australia as many wholesale investors take fewer risks,” he said. “In this tough funding climate, the Queensland Government has demonstrated tremendous leadership with its ongoing investment in the MRCF.”

Tropical health research initiative The Australian Institute of Tropical Health and Medicine (AITHM), based at James Cook University (JCU) in Townsville, will receive $42 million through the Australian Research Council’s Special Research Initiatives scheme, matching the Queensland Government’s funding commitment. The funding will be provided over four years and will go towards expanding the AITHM and consolidating planned research and training activities in the northern Australia region. AITHM has the three research priorities: health security and biosecurity; health in rural, remote, Indigenous and tropical Australia; and health in the tropics, regionally and globally. The Deputy Vice Chancellor of the Division of Tropical Health and Medicine, Professor Ian Wronski, said JCU’s location puts it in on the frontline for biosecurity and health security. “We are ideally placed to tackle issues including the prevalence of tuberculosis in neighbouring Papua New Guinea, as well as dengue fever, chikungunya, Japanese encephalitis and soil-transmitted parasites,” he said. “These are diseases that have a devastating effect on many developing nations in the tropics and also pose a threat to Australians, given our frequent interactions with neighbouring countries.” Plans for the funding include: • $25.5 million to fund tropical health research and training facilities at JCU in Townsville, Cairns and the Torres Strait • $10 million to fund a Translational Research Centre at JCU Townsville • $1.5 million to fund an Occupational Health Research Centre in Mackay • $5 million to fund network and general operating activities.

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Supporting Indigenous health A philanthropic gift of $10 million from Australian philanthropists Greg and Kay Poche will fund the establishment of another Poche Centre for Indigenous Health at the University of Melbourne. The Poches have donated over $40 million towards improving health outcomes for Aboriginal and Torres Strait Islander people, including the establishment of Poche centres at the University of Western Australia, Flinders University and the University of Sydney, which aim to contribute improve Aboriginal and Torres Strait Islander health and to close the gap in health outcomes between Aboriginal and non-Aboriginal people. The new centre in Melbourne will support Indigenous people to undertake PhDs and postdoctoral fellowships in health. Along with the Faculty of Medicine, Dentistry and Health Sciences, it aims to enrol 20 new Indigenous PhD students in health by 2020. “The mission of the University of Melbourne Poche Centre for Indigenous Health is to develop the next generation of Indigenous leaders who will influence the strategic directions of institutions, be mentors for emerging Indigenous leaders, build enduring partnerships and influence the health outcomes of Australia so that the gap in health status between Indigenous and other Australians is closed,” said Associate Professor Shaun Ewen, Associate Dean (Indigenous Development) at the Faculty of Medicine, Dentistry and Health Sciences at the University of Melbourne. Meanwhile, the Australian Government has announced that an implementation plan for the National Aboriginal and Torres Strait Islander Health Plan will be developed by the end of the year. Developed with input from Aboriginal and Torres Strait Islander health leaders and service providers, the Health Plan is a 10-year evidence-based framework designed to guide policy and program development to improve Indigenous health and achieve health equality by 2031.

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Ambassador

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A passionate advocate for science, Professor Lyn Beazley shares some of the exceptional and continuing contributions she has made to Australian science over a career that began with an affinity for biology. Australian Life Scientist: What inspired you to study science? Professor Lyn Beazley: I attended a state school in Britain and we had wonderful teachers for science. On one excursion we visited Down House, Charles Darwin’s house just outside London, and I had the opportunity to look through the microscope he used, see many of his specimens and his garden. I decided I wanted to be a biologist and I was lucky enough to attend Oxford University to study botany, but I changed to zoology. I completed my undergraduate degree, but towards the end I attended a lecture by a visiting professor from Edinburgh University, Professor Michael Gaze. He was working on repairing the brain after damage, particularly the visual system. We knew that some animals could repair

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their systems: fishes and frogs are very good at it, but humans are not. I thought I knew a little bit about fishes and frogs, and it sounded a wonderful PhD topic, so I moved to Edinburgh and completed a PhD on the development of vision and its recovery after injury. Neuroscience didn’t exist as a discipline when I first started. We were to be found in departments such as anatomy, physiology or pharmacology, and neuroscience became a discipline around me. I was at the beginning of a real surge of interest in neuroscience and the way it could be used, not only for theoretical advances but for practical help to improve human health - and I’ve been there ever since. ALS: What led you to move to Australia? LB: My husband and I moved to Australia

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in 1976; it was really to see a bit of the rest of the world. I saw a two-year visiting research fellowship at the University of Western Australia (UWA) advertised in Nature. I applied and was successful, so I came to a funded fellowship. At that time the National Health and Medical Research Council (NHMRC) was expanding its career fellowships program and I was lucky enough to be awarded a research fellowship. I then set up my own lab de novo. I had support from the university and applied for external funds from local funding bodies as well as the NHMRC. Over time I built up a substantial research group of about 30 people. Moving to Perth was an entirely positive experience for me. From the very beginning people were most welcoming and supportive. The biomedical

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FACE TO FACE | SCIENCE AMBASSADOR

SCIENCE AMBASSADOR | FACE TO FACE

“I am very keen to support getting more gender balance, whether it’s more women in engineering or encouraging more men in nursing or teaching... We need more balanced professions, we are getting there but there is a way to go.”

community were very inclusive and encouraging. I stayed as a Fellow until I moved across to a professorship at UWA in 1994 and then in 2006 I became the Chief Scientist of Western Australia (WA) on secondment from UWA. ALS: What sort of neuroscience research did you pursue? LB: During my PhD I investigated how the environment interacts with the developing nervous system, a theme I continued in my first postdoc in Britain. During development there is an exuberance of connections in the brain, more than you need long term, and then the inputs from the environment literally what you see in the case of the visual system - help ensure the survival of connections that are functional and the loss of inappropriate ones. I also studied recovery from neurotrauma. The retina, the lightsensitive sheet lining the back of the eye, receives light and converts it into electrical activity that is forwarded via the optic nerve to the brain. We knew that if that nerve is damaged in some animals it can regrow and reconnect to visual centres in the brain to restore near perfect vision. That is one of the big questions: why can a central nerve in an animal such as a fish or frog regrow but not do so in a human? We’re still struggling to achieve a similar success in mammals, including in humans. ALS: Your work changed clinical practice, can you tell us about this? LB: That was because of a serendipitous association with a wonderful professor at UWA, Professor John Newnham.

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He was working in the area of obstetrics and gynaecology, particularly concerned with the risks associated with preterm delivery. If a baby is born early, one of the most vulnerable systems is the respiratory one. The lungs need to be triggered to function at an earlier stage than they would normally do so and a great way to do that is with corticosteroids. A brilliant discovery by Sir Montague Liggins in Auckland was that corticosteroids prematurely mature the foetal lung, giving the baby a better chance of surviving being born early. So if a woman is at risk of preterm delivery, she is administered corticosteroids. These are transferred via the placenta to the baby so that if the baby is born preterm, the lungs are primed. But the issue was that the effects of the corticosteroids wear off over time. So if a mother was threatening to enter labour but did not, she might return and over time receive many courses of corticosteroids. High doses of corticosteroid can change patterns of neural development such as myelination, patterns of cell division and cell death. We studied the effect of a wide corticosteroid dose range in animals to estimate a dose that would be protective of the developing brain but still mature the lungs. It was amazing because in our first study, we took one look at the micrographs of the developing optic nerve in the corticosteroid treated and untreated groups and knew immediately that aspects of development were changed. That’s not to say that development could not catch up later, but it was much better if the influence was not detrimental from the

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beginning. Our work led to three clinical trials around the world and influenced the decision of setting the recommended dose of corticosteroid treatment. ALS: Do you feel passionate about educating people about science? LB: Absolutely! When I was at UWA I was very keen to give first-year lectures. I also ran a second-year course on development and a third-year course on comparative neuroscience. I feel very strongly that professors should engage with students when they first come to university. It was particularly important to me as we are still building up the number of women in senior positions almost everywhere, including in universities. I thought it was important to be a role model and to show students, as in my case, that you can, as a woman, have a partner, raise a family and still succeed in your career. Throughout my time as Chief Scientist, I was particularly keen to reach out to young people. I visited many wonderful schools here in Western Australia, and I spoke at a teacher’s professional development conference only last month. Engaging people with science is just so close to my heart. It has been a very important and a key part of my work, not only for the practical aspects in a university context of attracting honours students and PhDs, but much more widely than that. I’m passionate about sharing my enthusiasm for science and showing people how it fits into society, into industry, government and community. Whatever their background, people need to have an understanding of science because they will have to face issues such

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FACE TO FACE | SCIENCE AMBASSADOR

Professor Lyn Beazley with Dr Harry Butler AO at the Western Australian Museum at the event of Dr Harry's retirement from being Patron of the Friends of WA Museum.

as whether to immunise their children, whether to eat genetically modified crops, use of stem cell therapy or promoting renewable energy projects. We need to have an understanding of all of these areas and more to be active participating citizens of Australia and the world. ALS: And you have juggled a full-time career and family very successfully. LB: Yes, I have three wonderful daughters and I’ve had a very supportive partner right through. When I became Chief Scientist of Western Australia, I very much encouraged young people into the science area - both boys and girls - but there are some areas of science, particularly engineering, where we simply do not have enough women. Moreover, we tend to lose women from science, the numbers dwindling as their careers advance, and we are losing, therefore, some of the talent pool. I am very keen to support getting more gender balance, whether it’s more women in engineering or encouraging more men in nursing or teaching for example. We need more balanced professions; we are getting there but there is a way to go. ALS: You were Chief Scientist of Western Australia from 2006 until 2013 - how do you become Chief Scientist? LB: Well, in my case, I was approached I’m delighted to say. I accepted with great enthusiasm but also some caution because I didn’t know what it would be like,

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but it’s been a wonderful experience. I’ve been honoured and delighted to complete 7 years. It’s been amazing for me and I hope beneficial for my state and for Australia. ALS: Are there some highlights from that time? LB: There are a lot. One of them would be in terms of education. I’ve always supported the role of lab technicians in schools because I think doing science is not just a theoretical exercise, it’s very much a practical one too. So I’ve been involved in an initiative to set up a nationwide ‘hotline’ for lab technicians in schools to ensure they can talk to each other across the country, to introduce the best and safest procedures in schools and provide positive support for science teachers. That is one thing that I’m really happy to have achieved. Another initiative, this time at a local level, was to work for healthier estuaries in WA. Science really needs the public on board now because there are very big issues to address and we just don’t have enough scientists to tackle them. So we set up Dolphin Watch. The program, working with Murdoch and Curtin Universities, has trained nearly 700 individuals who are now monitoring the health of the Swan and Canning Rivers, particularly watching for dolphins but indirectly other aspects that would influence the health of the river system. This example relates to a more general

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principle that we can apply to support science projects in other areas. Setting up new apps, for example, so the public can interact with science and if they see something in the environment they can report it. These ‘citizen science’ programs I see as very important and increasingly will help science address issues, both local and national. I was also very much involved in the negotiations for the Square Kilometre Array, the radio telescope project that is arguably the largest science project that has ever been planned for the planet. It will be co-hosted by Australia, being mainly located in WA and in the Republic of South Africa. Throughout my time as Chief Scientist I argued strongly for Australia’s participation in the SKA. The project has already had various other terrific spinoffs; for example, we now have a super computer here in WA, which is available not only for radio astronomy but also for other areas such as predicting climate change, medical research, environmental and agricultural science as well as supporting the resources sector. This has all been part of building up science. I’ve described it like a table with four legs - industry, government, academia and the community. I’ve felt that my role as Chief Scientist was to facilitate interactions between these groups to make a difference in both the short and long term. ALS: Now that you have finished your term as WA’s Chief Scientist, what’s next? LB: I’m still very busy. People have very kindly asked me if I’d like to continue in many of the initiatives in which I have been involved. There are so many opportunities that have opened to me from being Chief Scientist that I can follow up without compromising the next appointee [who we now know is Professor Peter Klinken] to that important position. I’m a member of the board for Bionic Vision Australia and I’m also on the boards of two medical research foundations here in WA, one of which is addressing hearing loss in our community. I’m also still working with schools a lot. I’ve worked very closely with the WA

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SCIENCE AMBASSADOR | FACE TO FACE

Professor Lyn Beazley with Sir David Attenbourgh when a spider was named after him at the Western Australian Museum.

Museum for many years - I was a trustee for 7 years and am now Patron of the Friends of the WA Museum. One exciting

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thing that is happening in WA is building a new museum that will have science at its heart, along with social history and what it means to be West Australian. To play even a small role in helping to articulate the case for the new museum has been wonderful and we are really looking forward to seeing it open in 2020. Another initiative I set in motion was introducing FameLab into Australia. I plan to continue this association. This is an international program that is already up and running in 25 countries. I first encountered it when I attended the Cheltenham Science Festival in Britain, which is arguably the largest science festival in that country, and one component is the Famelab competition to find the best young science communicator worldwide. Weâ&#x20AC;&#x2122;ve just introduced the program to Australia - the British Council is very involved and itâ&#x20AC;&#x2122;s hosted by the WA Museum - 2014 is its first year here.

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One of the reasons we could run the program, which is based in Perth, was because His Excellency the Governor of Western Australia, Malcolm McCusker AC, made a philanthropic donation to help participants from across Australia to come to Perth - that made the difference between running the program and not. The winner, Dr Michael Smout from James Cook University, travelled to Cheltenham to compete in June. This is the sort of program that in the long term we should be supporting for the next generation because for me science communication is very important. Not just doing science, but learning how to communicate it and translating it to improve life on our planet. We are hoping to continue FameLab in Australia for at least the next 5 years; I hope it will then become embedded as part of our culture. Overall I trust I can continue to promote science as key to a better future on our precious planet. ALS

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AUSBIOTECH | VIEWPOINT

Call for tax reform as advanced manufacturing heads OS Industry is calling for further tax reform as the annual Biotechnology Industry Position Survey has revealed that Australian advanced manufacturing companies are increasingly heading overseas.

he annual Biotechnology Industry Position Survey (June 2014) has shown a worrying trend: advanced manufacturing associated with this industry of the future is following traditional manufacturing overseas. This has prompted calls for further tax reform to enable Australia to be internationally competitive. The survey, conducted each year by AusBiotech and supported by Grant Thornton Australia, showed 73% of respondent companies are manufacturing: 44% in Australia and 54% overseas, with a crossover of 25% that manufacture both in Australia and overseas. There was a slight rise from last year in the number of companies manufacturing, in addition to a clear shift to 54% of companies now manufacturing overseas compared to 36% recorded in 2013. As Australia’s window of mining construction-driven prosperity begins to close, and car manufacturing phases out, building Australia’s capacity as a technologically innovative country is vital for our economic future. Australia would benefit enormously from a well-targeted tax incentive to attract and retain R&D once it reaches commercialisation, and the resultant community and economic benefits. Specific policy settings are critical to aid the structural transformation of Australia’s economy towards high-tech, knowledgebased industries. These industries have the capacity to generate a globally competitive economy, increased exports and sustainable high-skilled jobs. Australia has a strong competitive advantage in ‘high-tech, high-cost, low-

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volume’ manufacturing to elaborately transform goods such as medical devices and bio-pharmaceuticals, and a burgeoning biotechnology and life sciences industry that is globally impressive by any comparative measure. It’s imperative that Australia takes action to remain competitive and relevant on the world stage, especially when other economies including the UK or Singapore are already reaping the benefits of their tax regimes and some Australian companies are moving operations to these nations to develop our IP. Maximising Australian innovation and reinvigorating the manufacturing sector in Australia largely depends on the existing R&D Tax Incentive being complemented with a tax regime that can secure Australia’s competitiveness for the future. AusBiotech and a number of industry bodies and businesses are advocating for the introduction of the Australian Innovation and Manufacturing (AIM) Incentive or a ‘patent box’-style incentive. This would help retain home-grown IP once it reaches commercialisation, as well as associated manufacturing, in Australia by offering a competitive environment. Supporters recommend that the federal government consider adopting the structure of the UK Patent Box model and adapt the policy to suit the Australian environment. Australia already supports the R&D phase of IP creation via the R&D Tax Incentive. The AIM Incentive is designed to capture the longer term benefits from IP creation by retaining the development and manufacture of locally patented products, and associated employment skills, through

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Dr Anna Lavelle, CEO , AusBiotec

a lower tax on the new activity created. It is not a subsidy or a support mechanism for this aspect of innovation, rather it is about creating an attractive environment to foster increased levels of investment and activity, leading to greater value in the economy. Other key findings of the Biotechnology Industry Position Survey 2014 include: • The industry’s outlook for the coming year is bullish with 81% of respondents expecting their business to grow and 70% of companies intending to hire more people. • The R&D Tax Incentive was very well received by the industry and its intact preservation remains the number one public policy issue within the industry. • The number of companies identifying the Australian operating environment (economic conditions and public policy) as conducive to growing a biotechnology company improved significantly this year, up to 38% (from 16%: 2012 and 24%: 2013). • Respondents remain cautiously optimistic regarding the change of government. A significant majority are opting for a ‘wait and see’ approach. • Positive shifts in investor sentiment both locally and internationally have translated into an improved funding position for many respondents. The number of companies holding less than 12 months’ cash decreased to 22% this year (37%: 2013). Interestingly, only 33% of respondents were definitely planning on raising capital in the coming year, while a further 17% flagged fundraising as a consideration. ALS

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BIOMARKERS | IMMUNOMODULATION

Finding markers

for inflammation and auto-immunity Graeme O’Neill

rofessor Mark Hogarth was a postdoctoral fellow at the University of Melbourne when his team cloned their first Fc receptor three decades ago. He says that, at the time, his chosen research field was something of an obscure curiosity. Today, a substantial part of a $50 billion industry revolves around the activity of Fc receptors. As of May this year, 352 monoclonal antibodies (mAbs) were either in clinical use or in clinical testing as new therapeutics. The life-saving or life-changing activity

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of many of the effective mAbs for cancer therapy, along with several anti-inflammatory and anti-infectives, ultimately depends on them binding a complementary Fc receptor on the surface of an immune-system cell: a macrophage, neutrophil, monocyte, dendritic cell, B cell or mast cell. Most leucocytes have multiple types of Fc receptor. “Therapeutically, Fc receptors are one of the most valuable classes of receptors,” Professor Hogarth said. “Monoclonal antibodies bind to their target in vivo and often their therapeutic benefit

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almost certainly involves harnessing or controlling powerful inflammatory processes induced by these Fc receptors - phagocytosis by macrophages, ADCC [antibody-dependent cellular cytotoxicity] by natural killer (NK) cells and inflammatory functions of mast cells.” The rapidly expanding arsenal of precision-targeted mAb therapeutics includes those engineered to shrink or destroy solid tumours, leukaemias and lymphomas, as well as anti-inflammatory mAbs to quench the unfriendly fire of

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IMMUNOMODULATION | BIOMARKERS

of antibody molecules - the flexible ‘stem’ of the antibody’s Y-shape - interact with complementary Fc receptors on the surface of leukocytes to induce particular responses from the immune system. Over the years, Professor Hogarth’s teams have been pioneers in many areas of Fc receptor research. “We were lucky initially to have a field that just about everyone else was totally uninterested in,” he said. “It’s been quite good to us - I guess it’s why we got the Gottschalk Medal in 1992.” The Australian Academy of Science’s prestigious Gottschalk Medal recognises outstanding medical research by young scientists within the first 15 years of completing their PhD. Over the 30 years since, the Fc receptors have gone from obscurity to being central players in immunity and help underpin the success of a valuable industry. RECEPTOR-TARGETED THERAPIES

debilitating auto-immune disorders like rheumatoid arthritis and lupus. Other mAbs have been manufactured to quell severe allergic disorders like hay fever, allergic asthma and eczema, and yet more to eliminate chronic viral infections like HIV-AIDS and hepatitis. FROM OBSCURITY TO CENTRAL PLAYER

Professor Hogarth heads the Inflammation, Cancer and Infection Laboratory at Melbourne’s Burnet Institute. He has devoted most of his career to exploring how the Fc domains

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Scientists and pharmaceutical companies searching to develop new therapies for cancer, chronic infections, and autoimmune and allergic disorders are exploring novel ways to manipulate Fc receptor function. In April 2012, Professor Hogarth and long-time collaborator Dr Geoffrey Pietersz, of the Burnet Institute and Monash University’s Department of Immunology, reviewed the state of Fc receptor research and discussed opportunities for new therapies in a paper published in Nature Reviews Drug Discovery. “There’s a big move today to exploit Fc receptors for therapeutic purposes,” Professor Hogarth said. “In the broadest context, Fc receptors are cell-surface receptors for antibodies, and they drive a very wide range of activities in human immunity.” In their Nature Reviews paper, Hogarth and Pietersz describe how antibodies evolved as soluble mediators of immunological resistance to invading pathogens. Over hundreds of millions of years, evolution has fine-tuned antibody

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activity, making them specific and efficient mediators of host protection. Sophisticated effector systems have co-evolved with antibodies and underpin their normally protective biological effects - Fc receptors present on immune cells activate these effector systems. Fc receptors are known for each of the major antibody classes, IgG, IgE and IgA, which bind to receptors Fc R, Fc R and Fc R, respectively. Professor Hogarth says while these Fc receptors perform distinct biological functions, they are all fundamentally ‘sensors’ of immune complexes: complexes of antibody and antigen such as an antibody coated autoantigen or allergen or cancer cell. As docking sites for antibody-antigen complexes, Fc receptors provide the humoral immune system with a cellular effector arm that links the adaptive and innate immune systems. By acting as receptors for antigen-antibody immune complexes, Fc receptors induce powerful responses that activate, regulate and modulate immunity. Fc receptors fall into two basic categories: activating and inhibitory, with the latter working by repressing the function of activating receptors. “There is enormous scope for manipulating Fc receptors with monoclonal antibodies or customdesigned synthetic molecules, to prime or direct the immune system assassins - like NK cells - to destroy established blood cancers and solid tumours or alternatively to block Fc receptor function in autoimmunity and allergy,” said Professor Hogarth. “There are two strategies to indirectly manipulate receptors by manipulating their ligands. These involve modifying the Fc domain of the antibody molecule to cause preferential binding to an activating receptor, or do the reverse and selectively bind to the inhibitory receptor. “In a global context, by manipulating antibodies in this way, you can manipulate the effector responses involved in pro- or anti-inflammatory activity,” he explained. “Depending on

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BIOMARKERS | IMMUNOMODULATION

the context, inflammation can be ‘good’ or ‘bad’. On one hand, Fc receptors can induce ‘good’, well-regulated inflammation - that’s how the immune system resolves infections and how vaccines work to induce immunity to infection or parasites. “On the other hand, ‘bad’ or destructive inflammation drives allergic reactions and auto-immune disorders like arthritis and lupus (systemic lupus erythematosus).” In autoimmune diseases, antibodies complexed with auto-antigens act as powerful inducers of inflammation, activating cells of the innate immune system such as macrophages, mast cells and NK cells that attack tissues. Failure of Fc receptor control also distorts the immune response of the adaptive immune system. In hay fever, antibodies complexed with normally innocuous antigens cause mast cells to release histamine. Professor Hogarth says blockading activating receptors can prevent immune complex inflammation in autoimmunity, and induce profound inhibition of tissue destruction. “One approach is to directly block receptors with anti-receptor antibodies, which induces them to turnover,” he explained. “Another is to use classical small drug molecules with molecular weights around 250 daltons.”

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PREVENTING TISSUE DESTRUCTION

After discovering and cloning several Fc receptors at Melbourne University with his student Margaret Hibbs in the 1980s, Hogarth worked with Tom Garrett and Peter Colman at the former Biomolecular Research Institute to solve the receptors’ structure in the 1990s. “Geoff Pietersz was able to use the structures, and some intuition, to design drug molecules to bind to the receptors. By this stage we had realised that Fc receptors are very important in the induction of destructive inflammation caused by IgG immune complexes Dr Maree Powell, who worked with me for 22 years, until last year, was very influential in this work. “She showed that if you can design molecules to interfere with Fc receptor function, you can actually prevent immune complexes from triggering tissue destruction. That was a paradigm shift, because the prevailing wisdom was that tissue destruction was pretty much due to the action of complement.” Complement proteins circulate in the blood and are usually activated by an antibody that has locked onto an antigen, after which they ‘complement’ the action of the antibody. “We tested our drug molecules in transgenic mice expressing a human Fc receptor - the FcγIIa receptor - and found they were very specific, and quite potent

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in the mouse, but not yet potent enough to take into human trials.” Hogarth says one particular receptor, the Fc IIb receptor, is primarily responsible for the immunomodulatory effects of Fc receptors. But recently, several overseas research groups have shown that in certain circumstances, some activating Fc receptors have a paradoxical ability to deliver inhibitory signals that inhibit immune responses. “That’s why we’re also interested in how antibodies work. By exploiting the dualism of Fc receptor function, we should be able to design small molecules or other antagonists that inhibit Fc receptor signals. With our increasing understanding of how these receptors function, it may also be possible under different circumstances to produce anti- or pro-inflammatory responses.” Hogarth says there is enormous scope for manipulating Fc receptors with monoclonal antibodies or customdesigned synthetic molecules. In this way, NK cells, for example, could be directed to destroy established blood cancers and solid tumours; or Fc activation could be inhibited to overcome pathological inflammation. Therapeutic monoclonal antibodies are a spectacular example of this potential. “Several anticancer antibodies - for example, rituximab - harness many of the Fc receptor-dependent destructive

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IMMUNOMODULATION | BIOMARKERS

Professor Mark Hogarth is a former director of the Austin Medical Research Institute, and now heads the Inflammation, Cancer and Infection Laboratory at Melbourne’s Burnet Institute. As a PhD student with Professor Ian Mckenzie at the University of Melbourne in the 1970s, he was one of the first Australian researchers to produce monoclonal antibodies. A world leader in the study of autoimmune inflammation, he has published more than 100 scientific papers.

inflammatory processes that are seen in the ‘bad’ inflammation in autoimmune destruction,” said Hogarth. Manipulating activating FcgR with engineered mAbs that will selectively increase binding to the activating receptor, or conversely, avoid inhibitory Fc receptor binding, could yield an even more destructive form of antibody therapy. Professor Hogarth says the flip side of antibody-Fc R immunotherapy is immunomodulation to repress ‘bad’ inflammatory processes. Since the inhibitory Fc R inhibits all activating receptors, antibodies engineered to selectively engage Fc R offer a new avenue for treating inflammatory diseases as diverse as IgE-dependent allergy and lupus. “Indeed we are very hopeful that we will soon have strategies to manipulate Fc receptors to quell the activity of the IgE receptor and fast-track allergic desensitisation therapy in life-threatening allergies. In lupus we could overcome autoimmune complex-driven activating IgG receptors.” VACCINE-INDUCED ANTIBODIES

Another area of promise for antibody therapies that harness Fc receptor functions is the treatment of persistent viral infections. “One of the problems with HIV infections is that the virus is outstandingly

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successful in evading the immune system,” Professor Hogarth said. “Much research effort has gone into developing vaccines against HIV, and recent trials point to a pivotal role for the Fc receptor function of antibodies in HIV resistance. Even neutralising anti-HIV antibodies depend on Fc receptor function for optimal effect”, which encourages the HIV research community to believe vaccine-induced antibodies could be the way to success. “We’ve been working in this area ourselves for a while, and we’re getting some interesting data around anti-HIV antibodies and Fc receptors,” Professor Hogarth said, adding that the National Institutes of Health (NIH) in the US had just announced it is seeking applications for grants to investigate the role of Fc receptors in HIV vaccine responses. Hogarth’s team has been working with Professor Stephen Kent, Dr Rob Centre and Dr Damien Purcell of the Peter Doherty Institute at the University of Melbourne and US collaborators on a project investigating how HIV evades vaccine-induced immunity and how the Fc receptor-dependent function of antiHIV antibodies might be optimised in vaccines. They plan to apply for one of the NIH grants. “So, once again we come back to the manipulation of Fc receptors as potential therapeutic strategies.” ALS

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MEDICAL DEVICES | 3D IMAGING

Bespoke biotech Additive manufacturing and 3D printing technology have a lot to offer makers of biomedical devices. Tim Dean

hey were a perfect match: dental appliance company Oventus had a problem in need of a solution and CSIRO’s Lab 22 had the solution on hand just waiting for a problem to show up. Oventus’s idea was for a new device to combat sleep apnoea, a disorder that occurs when breathing is disrupted during sleep. Sleep apnoea is a surprisingly prevalent disorder affecting around one million Australians and has been linked to insomnia, cardiovascular disease, diabetes and a slew of other ill health effects. Existing appliances that seek to treat the disorder by improving airflow through to the back of the throat have suffered from being overly cumbersome or uncomfortable. Oventus’s idea was for a slim new device that would aid breathing while being unobtrusive enough that it wouldn’t further disrupt sleep. The inventor, Dr Chris Hart, imagined a device in the form of a U-shaped mouthpiece that sits between the teeth and opens a pathway for air to reach the back of the throat unimpeded. It was a simple enough concept, but the design proved

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challenging for traditional manufacturing. This was in part because Oventus demanded the device be as slim as possible so it could be light and comfortable to wear yet sturdy and durable enough to last. Also, because each mouth is different, it had to be tailored to each patient. Mass production and bespoke devices aren’t typically a good fit. So, Oventus turned to the rising star of unconventional manufacturing: 3D printing. Specifically, they engaged CSIRO’s Lab 22, which was established in 2011 to develop the technology and to engage with industry to put it into practice. Teaming up with Oventus proved to be the perfect opportunity to show off what 3D printing is capable of right now. LAYER UPON LAYER

3D printing is straightforward in concept but revolutionary in its potential. While there are many individual 3D printing technologies, what they all have in common is that they build objects one layer at a time. Typically, the process starts with a computer

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aided design (CAD) file, which is a threedimensional representation of the object you want to create. This can be designed from scratch or derived from a 3D scan of an existing object. The object is then digitally sliced into thin horizontal cross-sections and the CAD file uploaded into the 3D printer. The material - commonly plastic, although metals and ceramics are increasingly being used - is then loaded into the printer in a fine powdered form. In the case of the Arcam 3D printer at Lab 22, an electron beam scans across the surface of titanium powder in the pattern of the topmost cross-section. This precisely melts the tiny pellets in the powder, bonding them together to form a solid. This thin slice of the object is then lowered and another layer of powder carefully raked across the top. The electron beam then repeats the process for each layer, lowering them one by one and covering them with more powder. Finally, the excess of loose powder is blown away - to be re-used in future print runs - and only the finished object remains.

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3D IMAGING | MEDICAL DEVICES

“It really depends on what you want to do. If you run a moving company, you should buy a truck, but if you want to commute you should buy a car.” The key, he says, is in picking the right technology for the job. Another term you might hear a lot is ‘additive manufacturing’, which Chad Henry, Additive Manufacturing Operations Manager at Lab 22, points out is best conceived as the overall process that has 3D printing at its core. “Additive manufacturing incorporates all the steps, including making the input material, designing the right file, uploading that file into the machine, the post processing and things like non-destructive inspection and heat treatment. All of that is additive manufacturing. 3D printing is just the printing step,” said Henry.

PRINTER POWER

ADDITIVE MANUFACTURING

The last decade has seen something of a Cambrian explosion of 3D printing technologies using a wide variety of approaches and materials. Many technologies use the same powdered-bed technique as Arcam, but others take different approaches. For example, Lab 22 also operates a coldspray machine, which shoots a fine stream of metal particles at ultrahigh speed towards a surface. When they impact the surface they form a metallurgical bond, building up layer upon layer. According to John Barnes, who holds the exciting title of Titanium Technologies Theme Leader at CSIRO, it is not likely that any one approach to 3D printing will end up dominating. Instead, each technology and every material has its strengths and weaknesses. Some are better at producing fine detail, while others can build things faster, while other printers can use multiple different materials simultaneously. “It’s a bit like asking someone whether you should buy a truck or a car,” he says.

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Traditional manufacturing processes, such as forging, casting or extrusion, are ideal for mass-producing thousands of identical objects, although they have their limitations. Often design is constrained by the minimum possible thickness of parts, or an inability to vary thickness throughout the object as required. Other limitations include the kinds of complex structures that can be cast, or the level of detail that can be built into or onto an object. Also, traditional manufacturing is relatively inflexible: if you wanted to make a lot of slightly different products, or a very short run of identical objects, then you often had to turn to handmade pieces, which could end up being prohibitively expensive. This is precisely the hurdle that Oventus ran into. It wanted to be able to produce a mouthpiece that was thinner than most traditional manufacturers could handle, and it wanted

each mouthpiece to be individually tailored to its user. One of the areas where 3D printing shines is in customisability, said Barnes. All you need to do is tweak the CAD file and print out your one-of-a-kind object. In fact, you can create a couple of dozen unique objects in a single print run. This kind of customisability was precisely what Oventus needed for its mouthpiece. After taking moulds of its patient’s mouths, it can tweak each device to suit. “That’s a unique attribute of the 3D printing technology that enables something to exist where it would have otherwise been cost prohibitive,” said Barnes. 3D printing also enables a greater level of detail than can be achieved with other manufacturing methods, such as injection moulding. One of the challenges with the Oventus mouthpiece, for example, was the complex internal structure. “If you look at the device itself, it has a hollow channel running through it in the shape of a T on its side. That’s where the teeth rest. Having that channel is essential to having the device work, as it allows the air to come in through the mouth, bypass the tongue and teeth, and move directly to the back of the throat. “It seems simple - you just want a hollow channel - but how do you make a hollow channel in a U-shaped piece with an oval opening to it? That’s not an easy thing to manufacture,” he recounted. Adding to this was Oventus’s desire for the mouthpiece to be as thin as possible, which made titanium an attractive material. With Lab 22’s expertise in 3D printing and particularly in titanium materials, all of these stringent requirements could be met, and be done economically.

Chad Henry is the Additive Manufacturing Operations Manager and the Titanium Stream Leader for the Titanium Technologies Theme within the Future Manufacturing Flagship at the CSIRO. He has previously worked as a Materials and Processing Engineer and Research and Development Engineer for 11 years in the aerospace industry. He has been a Research and Development Project Leader for five years, focusing on titanium and additive manufacturing technologies and delivering technologies from research and development to industry.

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MEDICAL DEVICES | 3D IMAGING

John Barnes has a Masters degree in metallurgical engineering from Purdue University in the US. He worked in the aerospace and defence industry in the US at Lockheed Martin Aeronautics and Honeywell International, including working on F-22 and F-35 stealth fighters. He currently leads the Titanium Theme within the Future Manufacturing Flagship at the CSIRO, working to expand Australia’s titanium processing industry by developing advanced additive manufacturing and powder production technologies for titanium.

LOW VOLUME, HIGH COMPLEXITY

There is currently a groundswell of biomedical device vendors actively exploring additive manufacturing for a wide range of applications. Ben Batagol is the business development manager for Amaero Engineering, which was spun out of Monash University to handle requests from the private sector to use its 3D printing machines. “We’ve had a lot of interest from the dental space - dentures, copings, implants, bridges - all things that have traditionally been made by hand in a dental laboratory. Every part is tailored to a patient and it fits very nicely into additive manufacturing, where you can quickly print 10 patients’ worth of parts in one job.” Batagol’s customers often want low volumes of highly complex parts, which have been either difficult to make or prohibitively costly using traditional manufacturing techniques.

Oventus’s 3D-printed mouthpiece for people with sleep apnoea. Made out of ultrathin titanium and coated with medical-grade plastic, the device is customised to each individual’s mouth for comfortable wearing.

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“We’ve got a range of customers who are doing parts by traditional methods, and they’re finding the process can be very expensive for low volumes, and they have high failure rates for very complex parts. They often had a lead time of over 12 months, whereas we were able to manufacture that part in a matter of days, and could produce large volumes in a much faster and easier and customisable manner.” IMPROVING IMPLANTS

Professor Tim Sercombe, from the University of Western Australia, has also been engaging with companies in the biomedical sector to investigate the potential of 3D printing implants such as artificial hips and cranial plates. One feature of 3D printing that gives it an edge over conventional manufacturing techniques is the ability to make the surface of the implant porous. “This then allows the bone to grow into the surface. With conventional manufacturing the best you can do is create a patterned surface, which allows some bone adhesion, but the porous structure will allow the bone to grow into it and give some mechanical fixation other than the screws.” Sercombe and his colleagues are currently working with titanium to make it more suitable for 3D printed implants. “One of the problems with titanium in the body is it’s too stiff. If you get the surface properties correct then bone will happily grow onto it and into it, but if the implant is too stiff, you run the risk of the bone dying off and the implant coming loose.” He is currently working on a new titanium alloy developed in China that

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has a stiffness roughly half of conventional titanium, and he’s confident they can continue to make refinements until they reach a material that is ideal for implants. REWRITING THE RULEBOOK

While 3D printing is changing the way biomedical products are made, it is also changing the way that designers have to think when it comes to conjuring them in the CAD program. “3D printing requires its designers to forget about everything they’ve learnt,” said Sercombe. “At the moment designers are having to temper their designs with concerns about manufacturability. They can’t design how they want to design because they have to make the thing at the end of the day. “Traditional manufacturing processes put all kinds of restrictions and constraints on the kinds of geometries that can be produced. If we can convince them to forget about how you’re going to make it, and design the thing how you want to design it, and we can make it, then that changes the paradigm significantly.” One of these limitations is the thickness that materials have to be when made with traditional manufacturing techniques. “Designers need to move away from the idea you have a uniform thickness on all walls,” added Batagol. “If you don’t need strength in a certain area, it makes sense to remove materials.” Additive manufacturing does have its limits. The surface finish on many 3D printed objects is not as smooth as forged or machined parts, thus requiring post processing to polish them up. 3D printers also aren’t well suited to mass production of identical objects, which can often be done far cheaper with conventional manufacturing. But 3D printing is finding a complementary role with traditional manufacturing and is likely to displace it in some areas, particularly in the biomedical space. For companies like Oventus, its experiment with 3D printing has proven to be a boon. It has been very pleased with the collaboration with Lab 22 and is currently on track to have its custom titanium sleep apnoea device ready for sale to patients in 2015. It may not be long before other biomedical device companies are also breathing easier thanks to the power of 3D printing. ALS

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Spectrometer With Merck Millipore’s Direct Detect spectrometer, the user is simply required to spot 2 µL of the sample, blank with buffer and read. There is no sample prep, no tedious standard curves and no messy cuvettes or liquid waste. The system exploits membrane technology

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Microbioreactor micro-Matrix offers an integrated, easy-to-use technology platform for the rapid handling and growth of large numbers of microbial strains,

Centrifuges

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PCR strip tubes SSI Ultraflux i PCR strip tubes enable users to amplify

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motely via web browser. It also has a mass concentration mode that approximates density in µg/m3. The product meets ISO 21501-4 and JIS B9921 and ensures compliance with an onboard pulse height analyser. Particle & Surface Sciences Pty Ltd

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CONFERENCE PREVIEW | CLINICAL BIOCHEMISTRY

Personalised, predictive,

preventive and participatory

The Australasian Association of Clinical Biochemists will hold its Annual Scientific Conference in Adelaide in October.

he upcoming Annual Scientific Conference of the Australasian Association of Clinical Biochemists (AACB) will focus on Clinical Biochemistry Supporting P4 Medicine - the four ‘Ps’ representing personalised, predictive, preventive and participatory. How the application of the four Ps can improve health outcomes while containing healthcare costs will form the major theme of the meeting. The term P4 was originally proposed by well-known American inventor and scientist Dr Leroy Hood. Hood has played a pivotal role in genomics and proteomics research by developing foundational instrumentation such as the automated DNA sequencer. He takes a holistic approach to biology and medicine, explicating a way of the future where technology will improve biological knowledge and P4 medicine will transform health care from a largely reactive discipline to a proactive one. Advances in genetics, genomics, pharmacogenomics and their associated technologies continue to bring new insights into preventative medicine. Updates on the impact of new technologies and research on laboratory medicine will be given by world experts at the meeting.

A few highlights include: • Professor Steven Wong from Physicians Choice Laboratory Services in the US will give a plenary talk on the role of pharmacogenomics in personalised medicine and personalised justice. • Professor Khosrow Adeli from the Hospital for Sick Children in Canada will give a plenary on patient safety and result reporting. • World leader of research into Alzheimer’s disease Professor Ralph Martins from the McKusker Alzheimer’s Research Foundation in Western Australia will give a plenary on the early diagnosis and prevention of Alzheimer’s disease. Two interactive workshops will also be held alongside the conference. A pathology workshop, aimed at developing ways of promoting the value of pathology, and a quality control workshop, which follows on from the QC workshop held in 2013. The closing date for early bird registration is 15 August 2014. For more information go to the conference website at: www.aacb.asn.au. Clinical Biochemistry Supporting P4 Medicine 27-29 October 2014, Adelaide, South Australia

SIMPLIFIED AND ENHANCED ANTIBODY CONJUGATION Are you having problems sourcing labelled antibodies? Are you encountering cross-species reactivity with your secondary antibody? The solution is to directly label your primary antibodies using Lightning-Link® Lightning-Link is: • Fast • Reliable • Unique • Easy To Use Lightning-Link features: • Over 40 labels • Label from 10µg to >5mg of antibody or protein • 30 seconds hands on time • 100% antibody recovery • Ambient temperature conjugation • Fast reaction times* * The antibody labelling kits come in two formats – Lightning-Link® and Lightning-Link® Rapid, with incubation times of 3 hours and 15 minutes respectively.

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PUBLISH OR PERISH

The return of our regular round-up of some of the best Australian research published each month in leading peer-reviewed journals. Archbold JK, Martin JL, Sweet MJ. UQ Towards selective lysophospholipid GPCR modulators.

Frazer IH. TRI, UQ Development and implementation of papillomavirus prophylactic vaccines.

Beattie AJ, Ehrlich PR. Mac Uni, Stanfd Uni Public outreach: Industries depend on biodiversity too.

Genovese P, Schiroli G, Escobar G, Di Tomaso T, Firrito C, Calabria A, et al. UQ TRI and collaborators Targeted genome editing in human repopulating haematopoietic stem cells.

Trends Pharmacol Sci 2014 May;35(5):219-26.

Nature 2014 May 29;509(7502):563.

Brooks AJ, Dai W, O’Mara ML, Abankwa D, Chhabra Y, Pelekanos RA, et al. UQ, St Vinct’s Inst Med Res Vic, Uni Melb and collaborators Mechanism of activation of protein kinase JAK2 by the growth hormone receptor.

Science 2014 May 16;344(6185):1249783.

Carlson TA. Mac Uni Orientation decoding in human visual cortex: new insights from an unbiased perspective.

J Neurosci. 2014 Jun 11;34(24):8373-83. Chen M. Uni Syd

Chlorophyll modifications and their spectral extension in oxygenic photosynthesis. Annu Rev Biochem 2014 Jun 2;83:317-40. Chen W, Foo SS, Rulli NE, Taylor A, Sheng KC, Herrero LJ, et al. Griffith Uni, Qld Arthritogenic alphaviral infection perturbs osteoblast function and triggers pathologic bone loss.

Proc Natl Acad Sci USA 2014 Apr 22;111(16):6040-5.

Nature 2014 Jun 12;510(7504):235-40.

Jegaskanda S, Ahn SH, Skinner N, Thompson AJ, Ngyuen T, Holmes J, et al. Uni Melb, Vic Infect Dis Ref Lab Down-regulation of IL-18 mediated cell signalling and IFN-g expression by the hepatitis B virus e antigen.

J Virol. 2014 May 28.

Jiang M, Gao M, Wu C, He H, Guo X, Zhou Z, et al. UNSW Lack of testicular seipin causes teratozoospermia syndrome in men.

Proc Natl Acad Sci USA 2014 May 13;111(19):7054-9.

Jex AR, Nejsum P, Schwarz EM, Hu L, Young ND, Hall RS, et al. Uni Melb, Griffith Uni and OS collaborators Genome and transcriptome of the porcine whipworm Trichuris suis.

Nat Genet. 2014 Jun 15.

Kazan K, Lyons R. CSIRO Plant Ind, Qld Intervention of phytohormone pathways by pathogen effectors.

Chong JJ, Yang X, Don CW, Minami E, Liu YW, Weyers JJ, et al. Westmead Hosp, Univ Syd and collaborators Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts.

Nature 2014 Jun 12;510(7504):273-7.

Cobbin JC, Ong C, Verity E, Gilbertson BP, Rockman SP, Brown LE. bioCSL, Univ Melb at Peter Doherty Inst Inf Immun Influenza virus PB1 and NA gene segments can co-segregate during vaccine reassortment driven by interactions in the PB1 coding region.

J Virol. 2014 May 28.

Cui J, Schlub TE, Holmes EC. Uni Syd AAn allometric relationship between the genome length and virion volume of viruses.

J Virol. 2014 Jun;88(11):6403-10.

Du D, Wang Z, James NR, Voss JE, Klimont E, Ohene-Agyei T, et al. Uni SA and collaborators Structure of the AcrAB-TolC multidrug efflux pump.

Nature 2014 May 22;509(7501):512-5.

Evans-Galea MV, Pébay A, Dottori M, Corben LA, Ong SH, Lockhart PJ, Delatycki MB. Murdoch Child’s Res Inst Cell and gene therapy for Friedreich ataxia: progress to date.

Hum Gene Ther. 2014 Jun 19.

J Immunol. 2014 May 1;192(9):4007-11.

Plant Cell 2014 Jun 10.

Kolesnikoff N, Attema JL, Roslan S, Bert AG, Schwarz QP, Gregory PA, Goodall GJ. Uni SA and SA Pathol Specificity protein 1 (Sp1) maintains basal epithelial expression of the miR-200 family: implications for epithelial-mesenchymal transition.

Mouradov D, Sloggett C, Jorissen RN, Love CG, Li S, Burgess AW, et al. WEHI, Uni Melb, Ludwig, QIMR, and collaborators Colorectal cancer cell lines are representative models of the main molecular subtypes of primary cancer.

Cancer Res. 2014 Jun 15;74(12):3238-47.

Myburg AA, Grattapaglia D, Tuskan GA, Hellsten U, Hayes RD, Grimwood J et al. ANU, WA Dept Parks Wldlfe, Vic Dept Env and Prim Ind, Uni Melb, Uni Tas and collaboators The genome of Eucalyptus grandis.

Nature 2014 Jun 19;509(7505):356-62.

North BJ, Rosenberg MA, Jeganathan KB, Hafner AV, Michan S, Dai J, et al. UNSW and collaborators SIRT2 induces the checkpoint kinase BubR1 to increase lifespan.

EMBO J. 2014 May 12.

Schuessler A, Smith C, Beagley L, Boyle GM, Rehan S, Matthews K, et al. QIMR Berghofer Med Res Inst, Qld Autologous T cell therapy for cytomegalovirus as a consolidative treatment for recurrent glioblastoma.

Cancer Res. 4 May 2014

Seim I, Jeffery PL, Herington AC, Chopin LK. QUT, Princess Alex Hosp Turtle ghrelin.

Nat Genet. 2014 May 28;46(6):525-6.

Soboleva TA, Nekrasov M, Ryan DP, Tremethick DJ. JCSMR, ANU Histone variants at the transcription start-site.

Trends Genet. 2014 May;30(5):199-209.

Stroud DA, Ryan MT. La Trobe Uni, Vic Stalking the mitochondrial ATP synthase: Ina found guilty by association.

J Biol Chem. 2014 Apr 18;289(16):11194-205.

EMBO J. 2014 Jun 18.

Kong SM, Chan BK, Park JS, Hill KJ, Aitken JB, Cottle L, et al. Garvan Parkinson’s disease-linked human PARK9/ ATP13A2 maintains zinc homeostasis and promotes α-Synuclein externalization via exosomes.

Thresher R, van de Kamp J, Campbell G, Grewe P, Canning M, Barney M, et al. Uni Canberra and collaborators Sex-ratio-biasing constructs for the control of invasive lower vertebrates.

Hum Mol Genet. 2014 Jun 1;23(11):2816-33.

Nat Biotechnol. 2014 May;32(5):424-7.

Lancaster GI, Langley KG. Baker IDI Endogenous, adipocyte-derived lipids signal the recruitment of proinflammatory immune cells.

Valdés-Mora F, Clark SJ. Garvan, St Vinc’ts Hosp and UNSW Prostate cancer epigenetic biomarkers: nextgeneration technologies.

Diabetes 2014 Jun;63(6):1844-6.

Larney C, Bailey TL, Koopman P. IMB UQ

Switching on sex: transcriptional regulation of the testis-determining gene Sry. Development 2014 Jun;141(11):2195-2205. Mason MG, Ross JJ, Babst BA, Wienclaw BN, Beveridge CA. UQ Sugar demand, not auxin, is the initial regulator of apical dominance.

Proc Natl Acad Sci USA 2014 Apr 22;111(16):6092-7.

Oncogene 2014 May 19;0.

Wong ES, McIntyre C, Peters HL, Ranieri E, Anson DS, Fletcher JM. Women’s Child’s Hosp, SA Correction of methylmalonic aciduria in vivo using a codon-optimized lentiviral vector.

Hum Gene Ther. 2014 Jun;25(6):529-38.

Wu LE, Sinclair DA. UNSW SIRT2 controls the pentose phosphate switch.

EMBO J. 2014 Jun 17;33(12):1287-8.

Tell the world about your event: email als@westwick-farrow.com.au

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EVENTS

DATES FOR THE LIFE SCIENCES CALENDAR The coming year is packed with exciting local and international events. Here’s a taste.

Towards precision medicine: Phenotyping human diseases in mice October 20-21, Canberra The 16th Frank and Bobbie Fenner Conference will celebrate the 10th anniversary of the Australian Phenomics Facility in conjunction with International and Asian Mouse Phenotyping Consortia and the Australian Phenomics Network. The meeting will cover the latest DNA sequencing technologies, developments in linking genomic variation in humans to disease phenotypes, the value of mouse models in validating these results in humans, data management and mining, coordinating national and international collaborations, and more. Awardee of the Nobel Prize in Physiology or Medicine in 2011, Professor Bruce Beutler from the University of Texas Southwestern Medical Center will give the keynote talk for the meeting at a public symposium at the Australian Academy of Science as part of the conference on October 20.

http://towardsprecisionmedicine-symposium2014.org.au

TRX14 - Translational Research Excellence Conference October 24, Brisbane

www.trx14.com.au

15th Australasian Plant Breeding Conference October 26-29, Melbourne

www.australasianplantbreeding.com.au/ Australasian Association of Clinical Biochemists 52nd Annual Scientific Conference October 27-29, Adelaide

www.aacb.asn.au/events/event/aacb-52ndannual-scientific-conference AusBiotech 2014 October 28-31, Gold Coast

www.ausbiotech.org Australian Society for Microbiology Annual Scientific Meeting July 6-9, Melbourne

10th Australasian Mutation Detection Meeting September 1-4, Daydream Island, Whitsundays

International Union for the Study of Social Insects international Congress (IUSSI14) July 13-18, Cairns

Joint International Symposium on the Nutrition of Herbivores/International Symposium on Ruminant Physiology International Conference September 8-12, Canberra

http://asmmeeting.theasm.org.au/

www.iussi2014.com/

16th International Amine Oxidase Conference July 15-17, Sydney

www.aoc2014.org/

http://wired.ivvy.com/event/MD2014/

www.herbivores2014.com/

International Association for Breast Cancer Research 2014 September 14-17 Sydney

AIDS 2014 - 20th International AIDS Conference July 20-25, Melbourne

www.iabcr2014.org

www.aids2014.org/

12th International Conference on Cognitive Neuroscience 2014 (ICON 2014) July 27-31, Brisbane

www.icon2014.org/

15th International Conference on Systems Biology (ICSB) September 14-18, Melbourne

www.icsb14.com

ComBio2014 September 28-October 2, Canberra

International Conference on Bioinformatics 2014 July 31-Aug 2, Sydney

www.asbmb.org.au

Australian Bioinformatics Conference October 11-12, Melbourne

http://incob2014.org/

2014 International Biophysics Congress August 3-7, Brisbane

http://bioinformatics.net.au/abic2014/ index.shtml

Science meets the market - ASiX August 20, Melbourne

Australian Genomic Technologies Association (AGTA) Conference October12-15, Melbourne

www.iupab2014.org

http://conta.cc/UkEk3g

www.agtaconference.org

Agriculture and Food Biotechnology Symposium October 30-31, Gold Coast

http://ausbiotechnc.org/program/AFBS

Lab Management Conference 2014 November 10-12, Sydney

http://conta.cc/1iq8VqE

Australian Health and Medical Research Congress November 16-19, Melbourne

www.ahmrcongress.org.au/ Sydney Cancer Conference November 26-28, Sydney

http://sydney.edu.au/cancer-research/ SCC2014/ Australasian Society for Immunology 44th Annual Scientific Meeting December 1-5, Wollongong

www.asi2014.org/

Australia Biotech Invest 2014 December 3-4, Melbourne www.ausbiotechinvest.com/ RACI National Conference December 7-12, Adelaide

www.racicongress.com/

World Indigenous Health Conference December 15-17, Cairns

www.indigenousconferences.com

Tell the world about your event: Tell the world email about als@westwick-farrow.com.au your event: email als@westwick-farrow.com.au

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Your NEW magazine is headed your way this September! ONE magazine TWO websites THREE eNewsletters

+ Lab+Life Scientist will bring together the best content from Australian Life Scientist and Whatâ&#x20AC;&#x2122;s New in Lab & Life Sciences. The latest news, technology advances, discoveries, developments and products relevant to the scientific research and life sciences, biotech, enviro, industrial, analytical and medical science sectors will come to you 8 times a year, and will remain FREE to qualified scientific and laboratory professionals. All current subscribers to ALS and WNIL will continue to receive Lab+Life Scientist starting with the September issue, which will officially launch at ComBio in Canberra. Your eNewsletter and website channels, www.lifescientist.com.au and www.labonline.com.au, will continue as they are.