Australian Life Scientist Sep/Oct 2013 by Westwick-Farrow Media

ComBio2013 PP100009448 ISSN 1448-9791

Insights into the lymphatic circulation 24

Vol 10 Issue 5 â&#x20AC;˘ September/October 2013

PL A N T SC IE N C E

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S TO RIES O F A PL AS TI C S U RG EO N

Contents FACE TO FACE

18 Bridging the gap between health and wellness With a continuing goal of delivering scarless healing to burn injury survivors, Professor Fiona Wood reflects on her career choice as a plastic surgeon, clinical researcher and the challenges along this path. COMBIO 2013

24 Lymphatic mispatterning Associate Professor Natasha Harvey heads to ComBio this year with a few years worth of results and an exciting new story of a protein called Nedd4 and how it could hold a key to better understanding the lymphatic vascular system.

26 CO2 causes turf wars

The planet is warming, but Professor Marilyn Ball’s research group at the Australian National University has found that rising carbon dioxide in the atmosphere makes cold-tolerant plants more susceptible to frost.

30 Nitrogen sustainability – a race against time The costs of the excessive fertiliser that is used to feed the plants that feed us – to farmers and the environment – is increasing. Developing a more sustainable use of nitrogen by reducing the levels of nitrogen fertiliser used in crop plants, whilst maintaining and improving yields, is a research goal of Dr Brent Kaiser at the University of Adelaide. AUSBIOTECH 2013

35 Bioeconomy in transition The Bioeconomy in Transition theme of this year’s AusBiotech will be a meeting of minds to share insights into the potential the biotech sector has in generating economic activity in Australia.

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Movers and shakers GrantWatch AusBiotech New products Publish or perish Events

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IN THE NEXT ISSUE OF ALS

• Next generation sequencing • 2014 Australasian Neuroscience

Society conference preview • Australasian Society for Immunology conference preview

Editorial deadline: 22/10/13 Advertising deadline: 22/10/13

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38 Challenges in the biotech business Establishing a small biotech company and getting products to market are some of the challenges facing the Australian biotech sector.

42 Personalised medicine According to David Randerson, Chief Executive Officer and Managing Director of TransBio and the Cooperative Research Centre (CRC) for Biomarker Translation, one of the big drivers of personalised medicine is the cost of healthcare delivery. The tailoring of diagnosis, prognosis, treatment and prevention of disease to an individual will bring benefits to the economy, society and people’s quality of life.

46 Biotech news Here we take a snapshot of news from the sector at the 2013 financial year end.

Cover image: Lymphatic vessels (red), blood vessels (green) and immune cells (blue) in embryonic mouse skin. This image was taken by postdoctoral fellow, Dr Genevieve Secker, working in Dr Natasha Harvey’s lab and was published as part of a manuscript in the journal Blood 119: 1293-91, 2012.

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he federal election was looming ever closer as this issue of ALS went to print, and the economy with its many challenges was a key area of debate. But that was back at the beginning of September. So, on to a less dated topic: the upcoming AusBiotech meeting, which will also have a focus on the economy - or more specifically, the bioeconomy. In our preview of AusBiotech 2013 (page 34), we hear about the potential role biotechnology and the life sciences can play in driving this country’s future economy. The economic transition that Australia is facing, to shift from relying so much on the resources sector and traditional manufacturing industries, is upon us. And new areas of growth, like the biotech sector, provide one pathway for us to take. Perhaps what’s needed are some new definitions or new ways of thinking about building the economy - an economy of knowledge that includes science, research and technology as an integral part of its framework. Australia has a rich and proud history in science and innovation, and the benefits of this investment surround us in our everyday lives - from advancements in health care and communications technology to what we consume and how we sleep. Building on this knowledge economy is not unrealistic for Australia - we have a strong knowledge base with lots of smart

people, we’re really good at generating new ideas and new technologies, we form strong collaborations through which basic and applied research can be translated into innovation and commercialisation, and we have many emerging companies. Getting research out of the lab and into the clinic, field or marketplace still seems to be a stumbling point for Australian research and innovation. As well as investment, a long-term perspective is needed. Working out how to support research and accelerate the innovation pathway will require changing the mindset of politicians, investors and even the general public, because outcomes in science and biotech do not happen overnight. For the sector to grow, long-term decisions and commitments need to be made all the way along the pipeline from education and training to translational research and commercialisation. Technology changes rapidly and this will continue to be a driver of the economy. And with a growing global middle class, the demand for a lifestyle that encompasses the benefits modern technology can deliver will only increase. The innovative areas of medical devices, plant science and agriculture, food manufacturing and technology, and, in time, bioprocessing, are areas Australia can mobilise to ensure we remain the ‘clever country’.

Susan Williamson INDEX OF ADVERTISERS AssureQuality 54 AusBiotech 34 Australian Scientific 29 Bio Processing Network 21 Bio-Strategy 15 BMG LabTech 37 Cryosite 55 Don Whitley 52

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MOVERS & SHAKERS

Fossil fragments rearrange marsupial evolution

Two fossil fragments found at the Tingamarra site in southeastern Queensland look set to overturn the conventional theory about the evolution of marsupials. Conventional wisdom holds that there was a single migration from the part of the Gondwana ‘supercontinent’ that became South America to the part that became Australia. One of the fossils is a 55 million-year-old ankle bone from a mouse-sized marsupial previously known only from South America. The second is a tooth from a formerly unknown species that shows similarities to fossils found in South America and, surprisingly, North Africa.

QIMR changes its name

QIMR

QIMR QIMR QIMR

“The origins of Australian marsupials suddenly got a lot more complicated,” said palaeontologist Dr Robin Beck from the University of NSW. “All the species of modern-day marsupials here are quite closely related. The species represented by the ankle bone belongs to an entirely different group - a group that we know lived in South America but, up until now, we thought never made it to Australia. The tooth is more of a mystery: are its origins in South America, Africa or somewhere else? “It is impossible to explain the presence of these new fossils in Australia using the single dispersal model. Instead, there may have been multiple movements of marsupials between South America and Australia.” The similarities between the fossil tooth and those of an extinct species recorded in Tunisia remain the tantalising subject of further research. For the moment, though, Dr Beck thinks the tooth and the ankle bone provide fascinating new information about the history of marsupials in Australia. “They mean that extinction has played a much bigger role in the story than we previously thought,” he said. “Some species became extinct in Australia but survived in South America. And perhaps the opposite is also the case - will there be discoveries in South America of typically ‘Australian’ fossils?” The work has been published in the journal Acta Palaeontologica Polonica.

QIMR BERGHOFER MEDICAL RESEARCH INSITITUTE

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Queensland businessman Clive Berghofer will give $50.1 million to the Queensland Institute of Medical Research (QIMR), making him one of Australia’s most generous philanthropists. As a sign of gratitude, and in recognition of Berghofer’s long history of support, QIMR will now be known as the QIMR Berghofer Medical Research Institute. Berghofer has previously donated more than $10 million to QIMR, which named its Cancer Research Centre in his honour in 2001. QIMR Director Professor Frank Gannon said this new donation made Berghofer one of Australia’s biggest individual contributors to medical research. “Simply put, Clive Berghofer is a truly great Australian. He has single-handedly transformed medical research in Australia and we will all benefit from his generosity,” Professor Gannon said. “Our research can only go from strength to strength with financial backing on this scale. Berghofer is a Toowoomba-based property developer and philanthropist. In 2006 he was made a Member of the Order of Australia (AM) for his service to the community through philanthropic support of medical research, sporting and educational organisations. He has also made sizeable contributions to Careflight, Red Cross, St Vincent’s Hospital, Toowoomba Hospice and the University of Southern Queensland.

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MOVERS & SHAKERS

2014

Academy Medal awarded The Australian Academy of Science has awarded Simon McKeon, AO FAICD, the 2014 Academy Medal for his contribution to Australian science and innovation. Hailing from Melbourne, McKeon was named Australian of the Year in 2011 for his philanthropic work. The Academy Medal was established in 1990 to “recognise outstanding contributions to science, by means other than the conduct of scientific research, by a person outside the Fellowship”. To date, seven people have received the prestigious award. “Mr McKeon’s extensive contributions to science and innovation, including chairing the 2013 Strategic Review of Health and Medical Research, leadership of the CSIRO Board since 2010, being Foundation Chairman, and now Patron, of Multiple Sclerosis Research Australia, and membership of the inaugural Bio21 Australia Board, make him a very worthy recipient of the Academy Medal,” said Academy President Professor Suzanne Cory. “In addition, he has championed informed debate on climate change and provided inspiring leadership in the community sector, especially in the areas of health and disability.” McKeon is also currently executive chairman of Macquarie Group’s Melbourne Office and chairman of Business for Millennium Development, a not-for-profit organisation that encourages business to engage with the developing world. The medal will be officially presented to McKeon at the academy’s annual flagship event ‘Science at the Shine Dome’ in May next year.

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Smart aquarium The experimental sea simulator, SeaSim, has opened at the Australian Institute of Marine Science (AIMS) in Townsville. SeaSim is a research aquarium that replicates, as closely as possible, the conditions of the open ocean, a reef lagoon or flooding rivers. It will help researchers better understand the impact of ocean warming and acidification, outbreaks of natural predators such as the crown-of-thorns starfish, and pollution. “It’s awesome,” said AIMS marine researcher Mike Hall. “When we started planning SeaSim we visited over 40 marine aquariums around the world to identify key attributes of the perfect research facility. What we’ve built takes the best in the world and adds new technologies and an incredible level of automation and control.” Opened by the Minister for Innovation, Senator Kim Carr, the construction of the $35 million facility was supported with capital funding from the Australian Government under the Super Science Marine and Climate initiative, and AIMS’ resources. “In each tank we can automatically control many parameters - from water temperature to ocean acidification to salinity to lighting to nutrients and water quality etc. “It’s not the be-all - it still has walls unlike the open ocean. But it will fast track marine discovery,” said Hall. John Gunn, CEO of AIMs, said researching the crown-of-thorns starfish would be a high priority for SeaSim. “We need to understand why starfish populations periodically boom, leading to massive reef destruction. Is it due to nutrients in flood waters or are more complex factors at play?” Other projects planned include creating small reef communities to induce coral spawning on demand to accelerate research, coral bleaching and factors that contribute to some coral communities surviving very high temperatures, developing a ‘model’ coral to help understand coral biology and modelling the impact of sediment, pollution, dredging and other water quality factors on marine life. The Australian Government committed a further $30.9 million over four years to AIMS in this year’s budget, including support for the facility to become fully operational in the 2013-14 financial year.

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MOVERS & SHAKERS

WA researchers target key plant pathogen Murdoch University researchers have uncovered an environmentally friendly way to address the significant threat to crop yields posed by root lesion nematodes. The researchers have developed a method for using genesilencing technology to control the plant pathogens. Research team leader Professor Mike Jones, a member of Murdoch’s Plant Biotechnology Research Group, said root legion nematodes are a hidden but major economic drain on the global agriculture sector. “Root lesion nematodes are major pests of agricultural, horticultural and industrial crops such as sugarcane. They invade and damage plant roots, making the plants susceptible to water and nutrient stress,” he said. “Not only do they rob host plants of essential nutrients while feeding, but they create entry wounds that leave plant roots susceptible to attack by fungi and bacteria in the soil.” The pathogens are responsible for a roughly 15% reduction in yields for key crops including wheat and barley, yet many farmers may not even be aware of the problem, Professor Jones added. The team’s method involves switching off certain genes in crop plants to block off the formation of proteins needed for the nematodes to complete their life cycles. A key advantage of this method is that it is clean. “If we are to adequately feed a global population expected to reach 9 billion by 2050, we need to find and develop environmentally sound methods that don’t damage our soil or threaten water quality,” Professor Jones said. “Our research is one step in that direction.”

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A new method for sequencing the genomes of cells found in the environment without cultivating them in a lab has been developed by Australian and US researchers. Associate Professor Aaron Darling from the ithree institute at the University of Technology, Sydney (UTS) and colleagues from the US Department of Energy Joint Genome Institute (DOE) and the University of Queensland developed the first enabling technology and new method of single cell genomic sequencing on a large number of cells. With over 200 uncultivated genomes from nine diverse habitats, this single cell sequencing methodology allowed the discovery and a first ever view of the genomes and lifestyle of 29 major groups of bacteria that are widespread in the oceans and the environment. © stock.xchng/profile/flaivoloka

Probing microbial dark matter

By analysing the sequencing data, Assoc Prof Darling reconstructed the evolutionary history of the microbes and mapped out where the sampled organisms lay on the tree of life and confirmed they were like nothing previously described by science. “We were able to characterise 29 major groups of bacteria that had never been characterised before,” Assoc Prof Darling said. “This is an amazing discovery because we’ve never been able to do single cell sequencing on a large number of cells before and this is a new technical advance. “It’s an exciting time to be working in the field of microbiology,” Assoc Prof Darling said. “Every surface of the planet is covered with microbes - they’re in the atmosphere, in the deep ocean subfloor and they’re in and on our bodies. “Before DNA sequencing was developed we had no way of knowing the intricate details of these microbes, but now [through this research] we have the ability to gain a greater understanding about the importance of microbial evolution on our planet and in everyday life.” This work was published in Nature.

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MOVERS & SHAKERS

Laureate Fellowships

and bionic eye funding © stock.xchng/profile/flaivoloka

Seventeen Australian researchers have received funding as part of the ARC’s Australian Laureate Fellowships scheme. Announced by the Minister for Innovation, Industry, Science and Research, Senator Kim Carr, the researchers will use the funding to tackle topics ranging from improved child health, language learning, quantum imaging in biology, harvesting energy from seabed soils and bacterial cell biology. “This scheme is specifically designed to attract worldclass researchers and research leaders who can build and strengthen our ability as a nation to make groundbreaking new discoveries,” Senator Carr said. Two of the Australian Laureate Fellows will undertake a mentoring role encouraging women to take up and continue with a career in research. “I congratulate Professor Glenda Sluga from the University of Sydney, who will receive the Kathleen Fitzpatrick Australian Laureate Fellowship, and Professor Tanya Monro from the University of Adelaide, who will be awarded the Georgina Sweet Australian Laureate Fellowship,” Senator Carr said.

More information on the Fellows and the scheme is available. Senator Carr also announced the federal government will provide an additional $10 million in funding to two Australian research teams working on the bionic eye - Bionic Vision Australia (BVA), led by the University of Melbourne, will receive $8 million and Monash Vision Group (MVG), led by Monash University, will receive $1.9 million. This funding is in addition to the $50 million previously provided and will allow the research program to be extended for another year. BVA is developing technology that implants a device in the rear of the eye (the retina) to enable vision to blind patients suffering from degenerative retinal conditions. MVG is developing a device to implant on the visual cortex of the brain, providing treatment for progressive blindness. Both the original funding and the funding extensions were awarded under the ARC’s Research in Bionic Vision Science and Technology Initiative, which was developed in response to the Australia 2020 Summit.

Soil scientist recognised The highest honour in the discipline of soil science, the prestigious Dokuchaev award, has been awarded to Professor Alex McBratney from the Faculty of Agriculture and Environment at the University of Sydney. Widely regarded as its ‘Nobel prize’ for soil science, the Dokuchaev award is presented by The International Union of Soil Sciences every four years. The award recognises Professor McBratney’s acheivements in basic research in soil sciences that have led to the development of new methods for capturing and disseminating of soil information. This, in turn, has lead to the sustainable management of soil in agriculture and the ecosystem. These methods have been eagerly adopted by research groups and practitioners worldwide and been applied to precision agriculture and digital soil assessment. The techniques of the team Professor McBratney leads form the basis of an international global digital soil map, GlobalSoilMap, which is funded by the Gates Foundation. The aim of the map is to provide information for policy and management decisions on food production,

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hunger eradication, climate change and environmental degradation. “I believe very strongly in the nexus between teaching and research - and in teaching-inspired research,”said Professor McBratney.“Several of the questions we have worked on arose from difficulties I encountered in explaining concepts to undergraduates - largely because the concepts were poorly thought out and had to be recast.” The award consists of an engraved medal, a certificate, an honorarium and financial support to attend the presentation in early June 2014 at the 20th World Congress of Soil Science in Korea.

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MOVERS & SHAKERS

GrantWatch Building Indigenous research capacity presence, administered from a central hub based at QUT, with ‘spokes’ of Aboriginal and Torres Strait Islander researchers located throughout Australia. Each ‘spoke’ will focus on one of four research programs: Indigenous Sociology and Knowledges, Indigenous Law, Indigenous Health, and Yuraki - History, Politics and Culture. The nine collaborating Australian universities involved in the network are Central Queensland University, Charles Darwin University, the Australian National University, University of Newcastle, University of Western Australia, University of Tasmania, University of Technology, Sydney, University of Melbourne and University of Wollongong. Five partner organisations - Aboriginal and Torres Strait Islander Healing Foundation, National Congress of Australia’s First Peoples, Ninti One Limited, South Coast Women’s Health and Welfare Aboriginal Corporation, and the United Nations University - have committed a further $2.1 million in cash and $3.4 million in kind towards the new network. More information is available on the ARC’s Special Research Initiative for an Aboriginal and Torres Strait Islander Researchers’ Network. © stock.xchng/profile/chrisgordo

The new National Indigenous Research and Knowledges Network (NIRAKN) has received $3.2 million over four years through the ARC’s Special Research Initiatives scheme. The Queensland University of Technology (QUT) will lead NIRAKN together with nine collaborating institutions across the country, the Australian Institute for Aboriginal and Torres Strait Islander Studies and five partner organisations. The network was opened by Australian Research Council CEO Professor Aidan Byrne, who said the aim of the network is to create pathways for Indigenous researchers from undergraduate to postgraduate studies and establish a pipeline of new researchers across institutions, disciplines and research areas of importance. “The initiative is aimed at creating a national collaborative network - harnessing the leadership of skilled and experienced university-based Indigenous researchers with strong track records who will build a research program to mentor those in their early careers, to improve their chances of staying on, filling research positions and pursuing successful research careers,” Professor Byrne said. The new network will be led by Professor Aileen MoretonRobinson from QUT and will have an interconnected national

NSW medical device companies receive funding Announced by the NSW minister for Health and Medical Research, Jillian Skinner, five medical technology companies are the lucky recipients of grants from the Medical Devices Fund. The Medical Devices Fund was launched in September 2012 and the allocation of funds was overseen by an independent panel chaired by Mary O’Kane, NSW Chief Scientist and Engineer. Covering a range of areas, the following five companies were chosen from a reported 147 applications: Elastagen - this company is developing a technology focusing on the medical repair and regeneration of the skin called elastatherapy.

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Endoluminal Sciences - working in the cardiovascular area, this company is developing a sealant-based medical device to prevent leakage from around current minimally invasive heart valve implants. HEARworks - spinning out of the Hearing Cooperative Research Centre and National Acoustics Labs, this company is developing further modules for their portable multifunctional instrument, HEARLab, which enables clinicians to assess hearing with automatic cortical tests. mobiLIFE - is developing a portable intravenous pump, mobiDRIP, which can be used to treat patients in the home by delivering continuous doses of antibiotics, chemotherapy, pain medication, nutrition. Saluda Medical - using neural recording technology, this company is developing an implantable device to treat chronic neuropathic pain that will focus initially on spinal cord stimulation.

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AUSBIOTECH | VIEWPOINT

Industry calls for innovative manufacturing incentive A growing chorus of respected business and economic voices is calling for the government to play a leading role in further tax reform to provide incentives for innovative manufacturing to support Australia’s future and keep us internationally competitive for attracting business.

y all early anecdotal accounts, the Research and Development (R&D) Tax Incentive is delivering on its promise to be a landmark tax reform. In its short life so far it has returned at least $45 million to ASX-listed biotechnology companies. Industry leaders are seeking to build on this success and complete the tax incentive suite to support Australian innovation. The R&D Tax Incentive remains a top priority for the life sciences industry; however, later stage biotechnology and medical technology companies that manufacture are not especially assisted by the R&D Tax Incentive because it phases out as a product or intellectual property (IP) reaches commercialisation. This is the point at which Australian IP is most vulnerable to being sold overseas along with the resulting community benefits. IP is highly mobile and can be easily separated from the jurisdiction where it was developed and migrated to low-tax jurisdictions. Industry is urging further tax reform to provide incentives for manufacturing and to encourage long-term investment in homegrown technologies, as well as pursuing a tax incentive to support export-oriented local production. Australia also needs to recognise the competition being provided by other countries, which, due to their tax treatments, are attracting our IP, after Australia has contributed the costliest R&D phase of innovation.

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For these reasons, nine nations (eight in Europe and China) have enacted ‘patent box’ regimes that provide incentives for firms to patent and produce - and to stay. The US is also in the process of introducing a patent box incentive. In 2012, a bipartisan bill with a 10% tax rate for qualifying IP income was introduced in the US House of Representatives. The most recent version of a patent box incentive has been introduced in the UK in April 2013, providing a 10% tax rate on revenues from patents (in contrast to a normal corporate tax rate of 26%). Analysis conducted in the UK indicates that the introduction of a patent box incentive leads to significant shifts in patent holdings towards those countries operating favourable regimes and away from other countries. While the UK Government estimated that its patent box will have an annual cost of about £1 billion, the increase in patent income, spillover benefits and other economic benefits should outweigh this cost. It was stated that adopting the patent box incentive in the UK would allow businesses to compete effectively in the global marketplace. To illustrate the point, GlaxoSmithKline has transferred most of its global IP to the UK since April 2013, announcing $800 million of new investment in the UK. GSK also intends to build its first plant in 40 years and is set to transfer 150 overseas research projects

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Glenn Cross, Acting CEO, AusBiotec h

to the UK to take advantage of the newly introduced patent box. Over the last two decades, Australia has been steadily losing its manufacturing sector to Asia, while governments continue to prop up unsustainable traditional manufacturing with millions of public dollars - innovative manufacturers with the jobs and economic support of the future, like biotechnology, are being left to ‘sink or swim’. Australia already supports the cost phase of innovation via the R&D Tax Incentive, only to lose out as companies take their IP offshore to lower tax jurisdictions. Support is growing for the proposed Australian Innovative Manufacturing (AIM) Incentive, a patent box incentive that will encourage high-tech innovation and advanced manufacturing to stay in Australia and attract overseas interest. Such a program would, unlike a direct grant, require companies to generate economic benefits for Australia before they would be eligible for the incentive. Manufacturing can and will play a role in the future prosperity of Australia and its strength will be in niche pockets. The R&D Tax Incentive is a great foundation for innovation to nation-build for Australia, but the tax reform story is not over for innovation. Australian policymakers and businesses need to do more to make manufacturing and investing in industries of the future more attractive and globally competitive.

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FACE TO FACE | FIONA WOOD

Bridging the gap between health and wellness Susan Williamson

Fiona Wood reflects on her career choice as a plastic surgeon, combining this with clinical research and the challenges involved in improving clinical outcomes of burns patients.

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FIONA WOOD | FACE TO FACE

ALS: How did you become interested in medicine and becoming a surgeon? Professor Fiona Wood: It was a combination I think of natural interest, aptitude and environment. At school I found myself in an environment with great teachers, particularly chemistry, physics and math - to the point that everything else fell away. I was initially interested in doing physics and math at university but with a bit of coercion - my brother was a couple of years ahead of me in medicine and my mother thought it would be a really good idea - I went to medical school. I enjoyed the whole atmosphere, the whole concept of being at university in London - it was brilliant. During med it became very clear to me that I was going to be a surgeon. In my second year I was plastic surgery junior at Great Ormond Street Hospital for Children in London. I continued surgical jobs all the way through from there. Increasingly, I focused on plastic surgery and I found myself in East Grinstead at the Queen Victoria Hospital in 1985. This was the home of the Guinea Pig Club in the Second World War - a famous burns unit where air force personnel who were severely damaged on their hands and faces underwent reconstructive plastic surgery. I spent a year there and that was when I was hooked into the burns area, as well as trying to work out how I could develop a research career around improving the outcomes of burn injury. ALS: Were there challenges in choosing surgery? FW: Being female was perceived to be a bit of a negative on the ledger. I was one of 12 women, and I was from Yorkshire. I was different going in and there were two choices: be different coming out or be a sausage coming out. And I wasn’t going to be jumping in the sausage machine! I did have to bite my tongue a lot. Working hard and being respectful of everybody’s contribution has been the way I have worked. You work hard and show that you can do it and people will support you. It’s not really rocket science, the way you approach people. One of my

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"I try to learn something from every person I treat. But do I achieve that? No." mother’s sayings is “more flies are caught with treacle rather than vinegar”. And I thought, well that’s the approach. Clearly I didn’t fit the mould, but I needed support to realise my aims. So if I could get support and I could give back then I would make more progress. It’s a lesson I learnt early. ALS: What led you into research? FW: I set the scene with research because it gave me the opportunity to step outside and do things differently, do things that were interesting. That was partly motivated to make sure that I was making progress but also because I wasn’t good at marking time. I wanted to be doing things that were more progressive. I did a Bachelor of Medical Science with a focus on neuroanatomy and at the end of that year I ended up in a field trip in East Africa, in Kenya and Tanzania. I looked at the impact of locomotion on the brain and brain development, various locomotor patterns and comparative neurobiology. That was really interesting and set the pattern with what I am interested in now. As I moved into my clinical years I was very keen on surgery and a bit slack on everything else. Rather than doing the standard 12 weeks of obs and gynae, I went to a government hospital in India and did a research project on maternal malnutrition, morphology and anatomy. By the time I arrived in Australia, I had connected the enquiry aspect of my head with the clinical and surgical practice - linking how to answer a question I was asking with how I could use that information to improve clinical care with a drive to improve patient outcome. It was about embedding that in my day-to-day work. I worked on cleft lip and palate as well as general plastic surgery, and burns was included in that. I did research into how the airway changes

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with the palate repair and how that influences the drive to breath. My first publication in 1989 was investigating the nerve supply in tissue-expanded skin as a plastic surgeon. I try to learn something from every person I treat. But do I achieve that? No. ALS: Can you describe your team’s involvement in the aftermath of the Bali bombing? FW: That was a set of certain circumstances driven by where we are geographically and I was part of the Australian response. I was working as head of the burns unit at the Royal Perth Hospital and how we responded came off the back of work we’d done previously. We know that every intervention from the point of injury influences the scar formed for life that’s one of our mantras. Clearly we don’t have a multidisciplinary dedicated burns team in every hospital in Western Australia (WA) - we only have a 10-bed burn unit at the Royal Perth and a 10-bed burn unit at the Princess Margaret Hospital for Children (PMH). And when you are in a low incidence but intensive care area, you’ve got to understand how you can outreach so that when a person is burnt, the burn team the person included - has the knowledge and we have the ability to talk to people to optimise every step of care. We spent a lot of time understanding how to ensure we had that information on the ground and the level of communication needed. We work on telehealth and we work with an outreach education program that’s been going since 1994. The Health Department was approached in the late 1990s by Woodside to discuss the disaster response around the north-west gas shelf. With the help of the Health Department and stakeholders

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FACE TO FACE | FIONA WOOD

Surgery being conducted after the Bali bombing in 2002.

across Australia we developed a disaster plan, the draft of which we ran through with an exercise funded by Woodside called Exercise Icarus. We learnt an enormous amount from that exercise. We then put that to the burns community across Australia and finalised the plan that we put to the Australian Health Ministers’ Advisory Council in June-July 2002. It was approved in August 2002 that we should run exercises and work out how to actually iron out the rough spots. But we never got to it because, of course, Bali happened in October 2002 so we did it for real. Geographically, we were the closet burn unit and that’s why we ended up with just under half of the patients from Bali. The other half were distributed between Adelaide, Melbourne, Sydney, Brisbane and Darwin, of course, which is our national triage centre where everyone did an amazing job. That’s why it unfolded the way it did - geography kind of drove it from a historical perspective and from a response perspective. ALS: And that’s when the spray-on skin captured people’s attention. How did that technology develop? FW: Basically, in 1985 I saw people growing skin cells into sheets in East Grinstead. It was very early days. The first people to use the cells of a person’s

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skin grown into a sheet were in the US in 1982. In 1990 there was a patient here in Perth who was very compromised. I was a registrar at the time and had heard on the radio that Joanne Paddle-Ledinek and Professor John Masterton had established a skin lab in Melbourne. To cut a long story short, I sent the skin from this patient to Melbourne, they grew it and John Masterton brought it back to Perth where we operated on the patient. She healed but she died with a secondary infection because by the time we did the operation it was five months post-burn that’s a long time to have open wounds with no skin. She had a fungal infection that was well established in her heart and we couldn’t eradicate it. Not long after that I became head of the burns unit. I was Director of the Burns Service of WA from January 1991 and I was obsessed with time. If I’d heard that radio program at 5 weeks post-burn

working very closely together to iron out the problems and one day we just looked at each other and said: “We should just spray this stuff on - well there’s a thought!” So we collected everything we could find that had a nozzle on it - throat spray, hair spray, nose spray, air brushing, we went to the art shop, the pharmacy, the anaesthetic trolley, and found all these different spray techniques and put cells through the spray nozzle system. We found the delivering nozzle on the top of a mouth freshener from Italy that, when clipped on a standard 5 mL syringe, enabled us to maintain 90+% viability of the cells coming through the system. It had to be a 5 mL syringe because it couldn’t generate the pressure - a 2 mL syringe could kill the cells by generating too much pressure. We had a lot of mouth freshener that we pulled the lids off. We were spraying skin onto wounds by 1995. Normally it takes three weeks

" We use the body as the tissue culture environment it’s cheaper, easier, more convenient ..." rather than 5 months, would the outcome have been different? Absolutely, categorically, I can say yes now because that patient has changed lives for many people who have come subsequently. So I started working with the team from Monash - it was costly and difficult and challenging. The skin would come back from Melbourne, arrive in Perth in the night and I would work on it in the lab through the night to have it ready for surgery in the morning. During that time I met Marie Stoner, a bone marrow scientist who was equally as crazy working through the night to get bone marrows ready. At the beginning of 1993 we received a Telethon grant to establish a skin lab at the PMH. We noticed that when the skin cell sheets were fragile and less developed, paradoxically they appeared to work better on the wound. Marie and I were

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for sheet of skin cells to graft. We were spraying skin cells that we grew in the lab onto wounds and getting results in 10 days, then in 5 days. For smaller wounds we developed a kit, putting elements of the tissue engineering process into a box, which harvests the cells in a 30-minute turnaround. ALS: So you don’t culture cells in the lab anymore? FW: No, we don’t use the lab as much at all now. For research and innovation driving forward we do, but from a practical point of view we can harvest skin cells from the dermal-epidermal junction and seed wounds with those cells using the ReCell kit. We use the body as the tissue culture environment - it’s cheaper, easier, more convenient, etcetera. If the wounds are prepared well then that is a better environment for the cells to grow in. They respond better and we get more

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FACE TO FACE | FIONA WOOD

rapid epithelial cover because the wound environment has appropriate signals for healing. Cell therapies have been an established aspect of our standard of care as far back as 1993 when we started using cell sheets and by 1995 we were using an aerosol-based system. We use cell-based therapies as part of our regime - it’s not an exclusive way we operate by any means, but we use it as part of our tool box. ALS: There was a lot of discussion about clinical trials in 2002 or the lack of them. Did you have to go back and conduct trials? FW: Yes. There were people who said there was no evidence base to support the work. This really fascinates me because for somebody to stand back and say there is no evidence and no prospective randomised trials to validate the technique is true in part but is a bit misleading. The work is based on basic science investigation and tested in animal models. We work in an environment which is really challenging to do prospective randomised trials due to uniqueness of each individual and the injury characteristics. How do we correct for all those things? We have published work using the skin graft donor site as a control wound with cells and no cells demonstrating a positive effect. We have also published a comparison of treatments randomised in scald injuries with positive outcomes. The treatment with cell therapies is one aspect of a complex series on

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interventions and we, and many others have now, have published the impact of the use in major burn injuries. In the US, an FDA trial is underway, supported by the US Armed Forces Institute of Regenerative Medicine - it is currently well progressed. Each patient is acting as their own control with small wounds that are very rigorously analysed in the face of a larger wound. From our point of view we have been working towards not only demonstrating that it’s effective and influences healing, but also trying to understand why. We are still in the thick of it; we’re still doing a lot of research to try and understand the mechanism of action. ALS: Have you been involved in commercialising the technology? FW: Marie and I established a company, Clinical Cell Culture, which has now gone on to become AvitaMedical, to commercialise the spray-on skin technology. At the outset Marie and I signed the intellectual property into the Foundation [the Fiona Wood Foundation] with the aim of supporting the ongoing research. It is now at the stage we are just starting to get momentum. In Munich earlier this year, AvitaMedical held a meeting with all the people internationally who use the technology and wanted to present their work. It was fascinating and stimulated further work. So 20 years on, people are using the technology in ways I hadn’t thought about, which is exciting. I’m still involved as a director, but my involvement is all around teaching new users and research protocols; but less and less as the interest is growing. ALS: What do you think about the progress being made in Australian life science and innovation? FW: Australia has got a lot of innovation, a lot of people thinking smart and a lot of great people, but how do we get to support them such that we can really accelerate this innovation pathway? I’ve lived this for 30 years, and that’s a challenge. If only we could work out how to support on all fronts from funding and the NHMRC, to working out how we

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can boost peoples’ interest in life science research because it’s the tomorrow. Our future lifestyles will be based on science and research. One of the things I’ve realised is that a lot of decisions that people make with respect to their lifestyle - obesity, diabetes, drugs, alcohol - means that we are running a health system that is creaking at the seams. I think our health system is constrained by funding, and that’s appropriate - otherwise it’s a black hole and where do we draw a line? How we collectively think smarter and support innovation is the key question. When it comes to innovation, driving innovation forward, I think we should stand back and say well done for anything that goes forward when we look at the sheer workload involved. Somehow we have got to bridge the gap between health and wellness and actually drive wellness so that when we do need healthcare we get not only the best in the world, we drive what is the best in the world. And I think that’s possible because I see some great work being done here - but a lot of it won’t see the light of day if we don’t change the balance. ALS: Finally, what’s in store for the future? FW: That brings me right back to the beginning - the neuroanatomy of the nervous system. I still want to understand the changes in the nervous system as a result of burn injury and how we can use that to heal to the pre-injury shape - that’s the aspirational goal. Will we be able to change the way we heal by neural stimulation? I don’t know whether that will be achieved in my lifetime but I do know we will contribute to the body of knowledge - understanding how we can manipulate the nervous system such that we can change the whole process and use it positively so that we get scarless healing, regenerative repair. We will be driving to see whether maybe at some point maybe we will change the way people consider healing and rather than a local thing it’s a systemic thing that can be influenced by neural control. And that will be exciting. ALS

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COMBIO | ORGANS AND PATTERNING

Lymphatic mispatterning Fiona Wylie

Natasha Harvey will head to ComBio this year with a few years’ worth of results and an exciting new story of a protein called Nedd4 and how it could hold a key to vascular networks and their problems.

erived from the Latin word for ‘fresh water’, lymph and its transport through a complex network of vessels and nodes helps the body maintain its homeostasis. The lymphatic vessels do this by returning tissue fluid and protein to the bloodstream. They also have a role in absorbing dietary lipids from the digestive tract and shuttling cells of the immune system to where they are needed. The lymphatic circulation has long been the neglected cousin in cardiovascular research and we still know surprisingly little about how the whole system is constructed and regulated. But, according to Associate Professor Natasha Harvey, head of the Lymphatic Development Laboratory at the Centre for Cancer Biology, SA Pathology, all that is changing as lymphatic research is going through a ‘boom’ time. A developmental biologist, Harvey’s

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research seeks to pinpoint key signalling pathways and molecules used in forming the lymphatic vascular system (lymphangiogenesis) during development. “The cardiovascular system, comprising the heart, blood vessels and lymphatic vessels, is the first organ network to develop in the vertebrate embryo,” she said. The growth, development and function of lymphatic vessels also tends to ‘go wrong’ in several disease settings in humans. Abnormal vessel formation manifests in conditions such as lymphoedema and vascular malformations, whereas excessive lymphangiogenesis is associated with inflammatory diseases and cancer. By identifying and characterising healthy lymphatic vessels, Harvey is aiming to find new therapeutic targets that block or promote the growth of lymphatic vessels. That is the plan anyway.

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REVISITING A SUCCESSFUL PARTNERSHIP

At ComBio, Harvey will present one of the major projects ongoing in her group. “For the last 4 years or so, we have been looking at the role of a ubiquitin ligase called Nedd4 in the development of lymphatic and blood vessels,” she explained. “Several years ago, we found that embryos lacking Nedd4 expression (knockout mice) have striking defects in cardiovascular development and since then have been trying to understand what Nedd4 is doing during that process. “This is being undertaken in collaboration with Nedd4 guru Professor Sharad Kumar, who I actually did my PhD with, so it is also great to be working with him again on this.” Nedd4 belongs to a family of functionally diverse enzymes involved in ubiquitination, a process of protein modification that is essential for many

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ORGANS AND PATTERNING | COMBIO

aspects of cellular regulation. The attachment of ubiquitin to target proteins marks them for degradation, regulates receptor internalisation into cells and directs protein trafficking within cells. Proteins such as Nedd4 thus have the potential to control cell function at multiple levels. For instance, Nedd4 regulates cell growth through the insulinlike growth factor 1 and insulin signalling pathways, and functions in the stability and trafficking of a range of other plasma membrane proteins. However, evidence from many sources suggests that Nedd4 has additional and important cellular targets. “Our current work on Nedd4 started when Sharad obtained the knockout mice and noticed that the embryos had a cardiovascular defect, so he asked us to take a look at them,” said Harvey. On first inspection, the embryos showed obvious oedema and haemorrhage, a clear indicator of problems with the development of their blood and lymph vessels. “We then looked further at the patterning and formation of the lymphatic vessels and could see abnormalities, particularly in the skin. The vessels looked sparse, spindly and unhealthy, and were formed into island-type structures. Basically, they were strikingly mispatterned,” Harvey reported. Because Nedd4 is a ubiquitin ligase, Harvey hypothesised that without Nedd4 being expressed, proteins within vascular cells were not being degraded normally or were signalling abnormally and impacting on vascular development. PICTURES TELL THE STORY

“This work has involved a lot of confocal microscopy imaging - often using wholemount stained embryos as we are really trying to get a 3-dimensional view of the vessel patterns. We have spent a lot of time working on techniques to visualise the vessels with as much detail as possible.” This approach allows Harvey’s team to really examine how the lymphatic vasculature is built during development - what pathways it takes, how it gets connected together as development

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Associate Professor Natasha Harvey currently heads the Lymphatic Development Laboratory at the Centre for Cancer Biology, SA Pathology. She completed a PhD and postdoc in the Division of Haematology at SA Pathology in Adelaide before a postdoc stint in the US at St Jude Children’s Research Hospital, where she focused on vascular development.

proceeds and where the signals that drive that patterning come from. The result is some quite stunning imaging that has been made possible by recent upgrades in imaging capabilities at the Centre for Cancer Biology. “We also work with primary endothelial cells, which we purify from embryonic skin and manipulate in vitro to look at cellular functions such as proliferation, migration and tube formation. Then, by exposing the cells in culture to different signals or by modifying their gene expression using siRNA, we can assess what genes regulate the processes we want to look at in these cells.” Indeed, Harvey’s group pioneered methods to purify, culture and transfect primary blood and lymphatic vascular endothelial cells, which have traditionally proven difficult to culture. Their work has paved the ways for new and improved assays to dissect gene function and signal transduction pathways in these cells ex vivo. THE IDEAL ENDPOINT

Harvey’s talk will represent a large body of work that she described as “just coming

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together at the moment - we are trying to get that last piece of the puzzle to publish a really strong and interesting story”. Their work has basically confirmed that Nedd4 is crucial for morphogenesis of the blood and lymphatic vascular networks during development. “We can see that Nedd4 is regulating pathways important for vascular development, although we don’t know exactly how yet and that is what we are now aiming to define. But, because Nedd4 is important for both blood vessel and lymphatic development, it really takes us further in understanding the signalling pathway required for construction of those vascular networks. “We are also certain that these pathways are in turn involved in disease settings, and by understanding the developmental growth mechanisms we hope to identify targets that could be modified to stop abnormal vessel growth such as in tumour metastasis or to promote the growth and repair of lymphatic vessels in conditions such as lymphoedema. It is a long way down the track, but that is the Holy Grail for our type of work.” ALS

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COMBIO | PLANT ECOPHYSIOLOGY

CO2 causes turf wars Graeme O'Neill

The planet is warming, but Dr Marilyn Ball’s research group has found that rising carbon dioxide in the atmosphere makes cold-tolerant plants more susceptible to frost.

rive south from Canberra on the Monaro Highway, through the rolling grasslands of the Monaro high plains, and you could almost be in the vast, treeless grasslands of the Central Asian steppes. In 1909, renowned Australian surveyor and botanist Richard Cambadge wrote of the Monaro grasslands: “It is remarkable that such an extensive tract should naturally be so destitute of trees and shrubs … the country is made up of clear undulating plains, with only a few isolated tree-clad localities.” It took nearly a century, but in 2002 plant ecophysiologist Professor Marilyn Ball’s research team at the Australian National University finally provided a convincing explanation about how the near-treeless grasslands of the Monaro have kept all but a few isolated pockets of woody invaders at bay. In her address at the ComBio conference, Ball will describe her team’s recent research into how the hardy, cold-tolerant grasses and megaherbs of sub-Antarctic islands are responding to rapid global warming, and increasing concentrations of carbon dioxide (CO2) and other greenhouse gases in the atmosphere - the work has not yet been published, but according to Ball, the news is not good. The work is focused on understanding structure-function relations in plants and how plant species differ in their physiological capacity to respond to changes in climate. “We study a range of plant communities from mangrove forests to subalpine eucalypt forests, to alpine vegetation in the subAntarctic,” she said. “We’re really interested in looking at temperature extremes - high and low. We restrict our studies to evergreen plants, because their leaves live for a long time and often have to cope with hostile extremes of temperature through the year.

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“For example, we want to understand how the adaptations that enable tolerance of freezing temperatures in winter affect the capacity to cope with hot, dry conditions in summer. Alpine environments typically experience wetter conditions than lower altitudes, so they go from freezing conditions in winter to hot, humid days in summer.” DEFENDING ITS PATCH

A decade ago, Ball’s team made the surprising discovery that the native grasses of the Monaro plains rule by creating a hostile microenvironment that alternately freezes or scalds the emergent seedlings of would-be woody invaders. Using a dry straw mulch to simulate a dense cover of live grass their thermal properties are identical, said Ball - the ANU researchers compared the survival of Snow Gum (Eucalyptus pauciflora) seedlings on bare ground versus soil with a full grass cover, through summer and winter. Snow Gums are one of Australia’s most cold-tolerant eucalypts. Near Charlotte Pass, in Kosciuszko National Park, they grow up to the snowline at an altitude of 1800 metres where winter temperatures can drop below minus 20°C in winter. Ball’s team found that seedlings growing in bare soil had a longer growth season than those growing with their roots covered by grass. Competition for below-ground resources was only part of the story. On bare ground, soil temperatures increase more rapidly in late winter and spring, giving the seedlings a longer growing season when soil moisture is abundant. After a year, the seedlings on bare ground had accumulated four times the biomass of seedlings grown with a grass or straw cover. Their more vigorous root growth in later winter translated to an

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PLANT ECOPHYSIOLOGY | COMBIO

“Once grass is established, it is a tenacious defender of its patch. Trees have no chance to establish unless a disturbance creates a bare surface.” Professor Marilyn Ball surveying the condition of the iconic cushion plant, Azorella macquariensis, in the alpine vegetation of sub-Antarctic Macquarie Island.

advantage in competing for soil moisture and nutrients in early summer. Seedlings with a grass/straw cover experienced greater temperature extremes during the year. Grass affects soil temperatures by reducing heat conduction into the soil in summer, so the seedlings entered winter with colder roots. Then, in winter, the insulating effect of the grass cover increases frost damage by lowering the temperature of the overlying air and extending the frost season. And in spring, grass cover retards soil warming, delaying the resumption of growth and reducing growth rates. The ANU researchers suggest these microclimatic effects explain how tree seedlings grown on bare ground can accumulate four times more biomass over the course of a year. “Once grass is established, it is a tenacious defender of its patch,” said Ball. “Trees have no chance to establish unless a disturbance creates a bare surface. We were stunned at just how potent those changes in microclimate can be.” Ball suggests the effect of grasses on microclimate may explain why it can be difficult to re-establish eucalypt seedlings in frostprone hollows after clear-felling. Self-sown or tube-grown seedlings initially grow well, but enter a phase known as ‘growth-check’ as a grassy ground cover develops. Growth-check has been attributed to root competition, but Ball’s team suggests it may also be due to effects of the grass cover on microclimate. FROST-TOLERANT SPECIES BECOME VULNERABLE

In plant ecology, it seems nothing is as simple as it first appears (see The Kermit Effect). Ball, who comes from Florida, originally intended to become an environmental engineer because she was interested in incorporating native vegetation in engineered water-management systems. But she changed tack after asking her teachers a simple question about mangroves: what’s the optimum mix of fresh and saltwater for a mangrove?

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THE KERMIT EFFECT

Global warming sceptics recently took heart from the findings of a joint CSIRO-ANU analysis of satellite imagery, which showed that the world’s arid and semiarid regions have become significantly greener since 1982, because of the CO2 fertilisation effect. The analysis, which found that Australia’s dry interior has become 11% greener during the study period, confirms a longstanding prediction about the response of woody plants to rising CO2 levels. Woody plants that employ the C-3 photosysnthesis system become more water efficient as CO2 concentrations in the atmosphere increase. As plants take in CO2 from the atmosphere, they lose water vapour through their open stomata - the tiny pores in the lower surface of their leaves. It could be called the ‘Kermit Effect’: it’s easier to be green when you’re getting more photosynthetic bang for your CO2 buck. But there’s a catch, according to one of the principals of the study - Dr Randall Donohue of CSIRO Land and Water. South African researchers have reported that the CO2 boost for woody plants, by increasing foliage cover, could allow them to shade out grass and invade grasslands. Woody plants increase fuel loads, so the end result could be a more flammable landscape. Another implication, says Dr Donohue, is that the increased foliage cover for woody plants makes them more sensitive to drought - their greater leaf area makes them more vulnerable to running out of water. “The foliage cover makes them more sensitive to changes in rainfall - logically, the changes means they will brown off more rapidly in drought, but green up quicker when the rain returns.”

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COMBIO | PLANT ECOPHYSIOLOGY

Professor Marilyn Ball and Dr Dana Bergstrom (Australian Antarctic Division) are conducting comparative studies on closely related cushion plant species to understand how differences in functional morphology relate to variation in tolerance of temperature and moisture extremes. Here, Professor Ball is collecting cushion plant samples high in the Chilean Andes (the work has taken her to elevations over 4000 m). Professor Ball received a PhD in Environmental Biology from the Australian National University (ANU) in 1982. Since 1990, she has led an ecophysiological research group in the ANU’s School of Medicine, Biology and Environment.

“Nobody knew,” she said. “How much flooding do the cypress swamps in the Florida Everglades require? Nobody could answer those questions.” Ball revels in the complex problems that plant ecophysiology throws up, because they can yield surprising, even paradoxical answers. Perhaps the most paradoxical finding to emerge from her team’s research is that, even as the planet warms, plants can become more vulnerable to frost injury, as the effects of frost are amplified by the rising carbon dioxide concentration in the atmosphere. “They get caught out, because they’re slower to acclimate to freezing temperatures in autumn, and they can also suffer damage because they de-acclimate more rapidly in late winter when grown under elevated CO2,” she said. Another complication emerged from their studies of woody plants in the high-altitude heathlands of the Blue Mountains, west of Sydney. Ball explains that plants that have adapted to habitats with freezing winter temperatures typically have small xylem vessels. Xylem vessels are the conduits for transport of water and nutrients from the roots to the stems and leaves. Maintenance of conduit function is essential for evergreen species. Reducing the diameter of xylem vessels reduces the risk of a freeze-induced air embolism - a breakage in the flow of the water streaming through the vessels. More than a decade ago, several overseas groups discovered that increasing CO2 concentrations alone increased the risk of fluid freezing in the tissues of frost-tolerant species because the gas increases the temperature at which ice nucleation occurs in their tissues.

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But this adaptation seriously affects the plant’s capacity to fix carbon by photosynthesis because of a physical law of diminishing returns that governs fluid flow through pipes: resistance to flow increases to the fourth power as the diameter of the vessel decreases. Halve the diameter of a vessel and resistance to flow increases by a factor of 16, so even a small reduction in xylem vessel diameter substantially reduces the amount of water the plant can draw up through its stem during photosynthesis. Ball says the reduction in conduit size is a trade-off that minimises the risk of frost injury at the expense of the plant’s ability to supply water to its leaves. Carbon cannot be absorbed through the plant’s open leaf stomata without water vapour escaping, so any reduction in water transport due to narrowed xylem vessels unavoidably reduces the capacity for carbon gain during warmer seasons. “You don’t see much shoot growth in winter, but winter photosynthesis is very important for growing the roots that will power the plant’s growth in the warmer part of year. So what goes on in winter is really important.” Ball says anything that reduces photosynthesis in winter - like the effect of elevated CO2 levels on frost resistance potentially has serious implications for vegetation in cold climates and may limit their capacity to respond with growth to climate warming. ALPINE VEGETATIVE COMMUNITIES

Preliminary results from the ANU team’s study of the alpine communities of the sub-Antarctic Macquarie Island - there are no woody plants on the island - indicate the plants are very sensitive to warmer, drier conditions.

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PLANT ECOPHYSIOLOGY | COMBIO

B-700 Series NEW

A study site on Macquarie Island showing the tussock grass, Poa foliosa, a dominant component of vegetation along the coastal slopes of the island. The research hut at Brothers Point can be seen in the distance.

“The pattern is similar to what we have predicted from our studies of woody plants in the Blue Mountains because the subAntarctic plants have limited capacities for water transport consistent with their adaptations to cold-wet environments,” she said. “We installed heat lamps that gently warmed the plants by around 2°C. This reduced the photosynthetic capacity of a common megaherb, while the dominant grass, Poa foliosa, responded with extra growth. “That’s a real concern for the iconic megaherbs, which have very large leaves but low capacity for water transport - they really suffer with an increase in temperature.” Ball says subAntarctic islands like Macquarie Island have a relatively mild oceanic climate, where the surface temperature of the surrounding Southern Ocean keeps temperatures relatively constant through the year. “You get more temperature variation in a single day in Canberra than you see in a year on Macquarie Island,” she said. Macquarie Island’s climate is constantly cool and wet, becoming cold and wet during winter. The island has no woody species, but some subAntarctic islands like Auckland Island, south of New Zealand, do have woody vegetation, and Ball says increasing temperatures will probably favour the growth of woody species and grasses, threatening major ecological changes. She says that complex interactions make ecological changes under a greenhouse-warming regime difficult to predict. “Nevertheless, our work has identified some basic ecophysiological traits that may make it easier to identify plants that might be advantaged by CO2 enrichment, and predict their responses to warming, and to identify other plants that might be at a disadvantage,” she said. ALS

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COMBIO | PLANT MINERAL NUTRITION

Nitrogen sustainability

- a race against time

Fiona Wylie

Take too much fertiliser, an inefficient crop, not enough land into the future to feed the world and more than a pinch of economics - and you have a recipe for disaster. Thankfully, Brent Kaiser is quietly confident that scientists like him can contribute to a more sustainable future.

“H

ouston, we have a problem” … it is called nitrogen and most of it is ending up down the drain. The nitrogen in question comes from the excessive fertiliser used worldwide to feed the plants that feed us, and the problem has arisen because, like many other things involving humans in our post-modern, post-industrial and post-sanity world, the whole natural balance is out of whack. A COSTLY PROBLEM

In an ideal agricultural world, plants would get all the nitrogen they need from the soil, helped by the host of clever bacteria that can ‘fix’ nitrogen from the atmosphere or convert it into a plantfriendly form from decomposing plant and animal matter. However, over the

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last 60 years or so of humans striving for stronger plants and higher-yield cropping, the ideal has faded in terms of the natural nitrogen cycle. We have bred nutrient-hungry monoculture crops like maize, wheat, rice and canola to be increasingly dependent on an organically rich soil that exists quite rarely in nature. To thrive and produce the food we require, these crops now depend almost entirely on what we put into the soil. These higher-input requirements ultimately drive an increasing demand for inorganic nitrogen-based fertilisers that are cheap to produce and easy to use. Unfortunately, the uptake and use of such fertilisers by most crop plants is inherently inefficient due to a combination

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of agronomy-, soil- and plant-dependent factors, resulting in higher amounts needed more often in an ongoing and vicious cycle of cost and waste. Indeed, after seed, nitrogen fertiliser is the single-biggest dollar cost to crop farmers - increasing the efficiency of nitrogen use by plants, even by 10%, would save farmers a ‘ton’ of money. The environmental costs associated with our ever-increasing fertiliser use are also large, although harder to quantify, as Associate Professor Brent Kaiser from the University of Adelaide attests. “The numbers are very scary on how much nitrogen we use to grow what we eat,” Kaiser said. “Every year that we put nitrogen fertilisers into the ground (~120 million tonnes per annum globally),

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PLANT MINERAL NUTRITION | COMBIO

we are putting more and more reactive nitrogen into the environment.” The problem is that a typical cereal crop will take up only 30-50% of the nitrogen supplied in fertiliser. While soil microbes compete with some of the remaining nitrogen, a significant amount is either released into the atmosphere as nitrous oxide, a major greenhouse gas, or simply leached into the groundwater in the form of nitrates. From there it seeps into the rivers and streams, and eventually into the sea. “Of course, other organisms down the chain can use this extra nitrogen. However, very efficient and competitive users like algae thrive on it, leading to eutrophication of aquatic ecosystems. Combined with extra phosphorous in the soil solution that is also coming out into the groundwater, the conditions can result in huge algal blooms that eventually make the water so hypoxic that fish and other sea life struggle to survive,” explained Kaiser. The annual release of agriculturally derived nitrogen, combined with other forms of post-industrial nitrogen pollutants (nitrogen oxides) caused by the burning of fossil fuels, has the potential to create significant long-term environmental havoc. MANAGING A NITROGEN DIET

For the last 10 years Kaiser and his team have focused on nitrogen transport and defining the biological mechanisms by which plants take up nitrogen and

The impact of nitrogen fertilisers on maize growth. Source: CIMMYT - International Maize and Wheat Improvement Center.

move it around between plant cells and tissues as they grow and produce seed. Basically, they are trying to make agricultural crops better managers of their own nitrogen diet. “We have a basic idea of how nitrogen gets into the root and is distributed within the plant," Kaiser said. "However, we have a poor understanding of how this process is regulated at the molecular level and where better efficiencies in nitrogen use can be achieved as the plant grows, senesces and ultimately produces its final yield.” According to Kaiser, the postgenomic era has revealed a lot more than we used to know about plant genes and systems, particularly with respect to how plants use nutrients. It has also provided us with tools to investigate quite complex plant regulatory systems. “However, much of the work was

Associate Professor Brent N Kaiser heads a small research team in the School of Agriculture Food and Wine at the Waite Campus of the University of Adelaide. He teaches viticulture and plant biology and is program coordinator for the wine science degrees within the school. He completed a PhD in plant biology at the Australian National University followed on with short postdoc placements at the University of Nice-Sophia Antipolis, University of British Columbia and the ANU. His current research interests focus on the sustainable use of nitrogen by crop plants and the symbiotic relationship between legumes and soil bacteria.

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and is done in model non-agricultural plant systems, and taking those results to an agriculturally important crop grown in the field has told us that we actually know very little. Many things change when genetic, environmental and management interactions are evaluated together.” Using a combination of approaches,

including traditional gene and protein profiling in plant tissues, expression of cloned transport proteins and wholeplant physiological analysis, Kaiser’s team have embraced maize as their model of choice to focus on improving nitrogen use in agricultural crops. “As maize is one of the biggest users of fertilisers globally, there is hope this research will contribute to direct improvements at the farm level that improves production while reducing nitrogen use and its potential loss to the environment.” MAPPING THE MAIZE NITROGEN NETWORK

The team is assembling interesting results and ideas about how plants use nitrogen in what they call the nitrogen transport network. “Our goal is to develop a road map of key genes and proteins involved in nitrogen transport and its regulation - focusing on where they are, when they are off, when they are on across the developmental growth cycle. Then, once we have that road map for our

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COMBIO | PLANT MINERAL NUTRITION

experimental plant, we can start to look at natural variation among maize inbreds and hybrids and how those networks interact and respond to different environmental cues," Kaiser explained. "Ideally we would like to work out the key genes or pathways associated with the best plant vigour from a low nitrogen input context. So, if we could, for example, identify key genes that are on at a certain stage of maize development or when maize nitrogen demands are high, then we can start to manipulate the nitrogen network to improve uptake, storage and/ or remobilisation.” SIMPLE MODELS HAVE THEIR PLACE

Kaiser also uses model systems such as Xenopus laevis oocytes to work out the transport properties and exact functions of individual genes and proteins involved in moving nitrogen in and out of plant cells. “This is one aspect that is rather lacking in the field … knowing at a system level what things actually do or can do,” he added. “There is a real efficiency to be gained in taking the systems biology findings back to the protein components to identify functionality.” For the last seven years, Kaiser and colleagues at The Australian Centre for Plant Functional Genomics, have worked in collaboration with large US seed

An example of an algal bloom caused by the run-off of nitrogen from nearby farms in a canal in Wageningen, the Netherlands.

company DuPont Pioneer whose major interest is finding a trait or traits in maize that will reduce fertiliser requirements by up to 30% while producing the same or increased yields for the grower. This means less cost for the producer, potentially less pollution and a competitive edge for the company.

CONTRIBUTING TO GLOBAL WARMING

Nitrogen fertilisers contribute to global warming by being a source of greenhouse gases - they increase nitrous oxide emissions from the soil into the air. This accumulation of nitrous oxide will only decline slowly because of its long half-life (150 years). Nitrogen fertilisers also add to methane emissions by reducing the capacity of soil microorganisms to absorb methane. And they contaminate groundwater. In addition to this, the production process itself for inorganic nitrogen fertilisers is also a global environmental issue. It is energy intensive and adds to global warming through carbon dioxide emissions. “Converting atmospheric nitrogen into a form usable by plants is a highly energy-intensive process that has traditionally used fossil fuels as an energy source. So, not only are we using a non-renewable resource that is itself associated with greenhouse gas generation for fertiliser production, we are also generating a humungous amount of greenhouse gases in the process. On the other hand, we need this nitrogen to grow plants to eat!! So we are sort of caught in a not-sodesirable circle.”

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TAKE-HOME MESSAGE

“In summary, we are looking for conserved genes that can become a representative signal of nitrogen use in the plant,” said Kaiser. In this context, Kaiser and his team hope to establish maize as a proper model system for use by others. He is also passionate about convincing other plants scientists that working on a crop that is of direct application is the way to go. “Experimental biology such as ours can then be immediately and directly applied to a crop that you put in the soil for food production.” In terms of the original problem, Kaiser is sure that the breeders and basic scientists working closely together will get there in producing more nitrogenefficient crops. He does remain a little worried, however, when the talk turns to the staggering rise in global population expected within the next 30-50 years … and suggests that, perhaps, it is time to start loving those nitrogen-sustainable crops including chickpeas and algae a whole lot more. ALS

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BUILDING BIOACTIVITY | AUSBIOTECH

Bioeconomy

in transition

Susan Williamson

This year’s AusBiotech conference will focus on the transformation of the Australian biotech industry, following its evolution and the application of its bioactivity across areas such as agriculture, food technology and health. In this preview we provide a bumper sample of what’s in store for Brisbane at the end of October.

‘

ioeconomy in Transition’, the theme of this year’s AusBiotech conference, recognises the potential the biotech sector has in generating economic activity in Australia. “One very interesting and often misunderstood thing is that on a global scale Australia has a very large life science sector. And it’s a broad sector - agriculture, industrial, and medical devices and diagnostics,” said AusBiotech Acting Chief Executive Officer Glenn Cross. FILLING THE MANUFACTURING GAP

Cross believes the biotech sector has the potential to fill some of the gaps left by the demise of traditional manufacturing areas such as textiles, footwear, heavy manufacturing and more recently, the automotive industry. “There are two areas that the life sciences and biotech sector offers to fill this gap, that is food manufacturing and technology, and medical devices and

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diagnostics,” said Cross. “Manufacturing is a key area in which biotech can transform the Australian economy.” Food technology and manufacturing will be a key component of the conference, with a full day reserved for agriculture and food technology. Medical devices and diagnostics will be covered across a number of sessions including a session on personalised medicine (see below). “This is a key area for driving the life sciences sector forward,” said Cross of medical devices and diagnostics. “It has the ability to absorb skills from the automotive industry as well as add a new manufacturing and skills base through areas like nanotechnology, biomaterials and small-scale manufacturing.” Add to this the slowdown in the resources and mining sector, and the opportunities increase. “We are seeing increasing interest from the Australian resource investment

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community to support biotech,” continued Cross, adding that the risk profile in life sciences is similar to the resources industry. “We are seeing an increasing level of interest from private investment - high net-worth individuals and people who would traditionally invest in the mining sector plus institutional funds.” Cell therapy manufacture and bioprocessing is another area of potential growth, although it is a few years behind medical devices and diagnostics. But progress is underway, with global bioprocessing giant DSM opening a new biopharmaceutical plant in Brisbane during the conference. This will be the first commercial bioprocessing plant in Australia and sets up another avenue for the bioeconomy to expand into. THE ASIAN OPPORTUNITY

Another key issue for Australian biotech is Asia. Australia is in a strong position

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AUSBIOTECH | BUILDING BIOACTIVITY

“Our sector takes a long time for creation of wealth and we believe there should be personal tax incentives for people who are prepared to put their money into a company and leave it there for a long period of time.”

as the largest player in the Asian biotech cluster - and Asia is currently the thirdlargest biotech cluster on the global playing field after the US and Europe. Cross predicts the Asian cluster will, over time, become as big as the other two and says this has been a focus for AusBiotech over the last few years. “AusBiotech has been making a strategic push for Australia to become a key player in the Asian biotech sector,” he said, clarifying that at the moment this push is primarily across human health and agriculture. “We see these two areas as key for Australia to build a successful future in the life science sector in Asia.” Australia is placed well to drive innovation and R&D, which are being recognised as important in Asia. The potential exists to attract investment from Asia and Cross said now is the time for Australia to develop its industry. “We have one of the key biotech industries in the region, but that won’t last forever,” said Cross. “China especially, and perhaps India, are going to have significant industries of their own so now is the time. Australia needs to make sure it is well placed so that we maintain our position of prominence in Asia.” THE PATENT BOX

Encouraging the government to contribute to the biotech sector through public tax policy is an area of focus for AusBiotech. These new initiatives are about creating a different model and a new way of thinking about building the economy. Two new tax incentives that AusBiotech is working on - innovative manufacturing

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incentive and a patient investor incentive - are one way of providing support for the biotech sector in becoming a key transformer of the economy as Australia moves away from relying on the resources sector. These tax incentives provide benefits to the sector that then flow onto the economy by generating growth around advanced manufacturing, agricultural and biotech companies. “We have broad opportunities in life sciences and agriculture but we also have the opportunity to replace old manufacturing with new advanced manufacturing, and most of that’s going to come from our sector,” said Cross. “There’s not going to be a lot of advanced manufacturing opportunities in Australia other than through nanobiotech, medical devices and diagnostics.” AusBiotech has been doing some solid work in encouraging the government (and the coalition as this issue of ALS went to print) to introduce an innovative manufacturing incentive through the tax system. According to Cross, eight European countries and China have introduced such an incentive, and the US is about to introduce it. “Typically, in Europe, they’ve reduced their corporate tax rate on the manufacturing incentive from 30 or 40% to 10 or 15%,” said Cross. “So we would be looking at a significant reduction in corporate tax rate on product manufactured as an innovative product that holds a patent, especially where that patent may have resulted from R&D conducted in Australia and where the R&D tax incentive was part of that input.”

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AusBiotech was finalising a position paper on this incentive as this issue of ALS went to print. Cross had had initial discussions with the current government and coalition to ensure that both parties were aware of the policy. “It’s called patent box in Europe and it is known as a patent box policy,” said Cross. “It is across the board, not just in the life sciences; it’s a broad-based innovative manufacturing incentive tax.” Cross said the R&D tax incentive has resulted in an increase in clinical trials in Australia, which in turn has grown the sector by creating more jobs in that area. An important aspect of the manufacturing innovation incentive is that it will provide companies with an incentive to stay in Australia rather than move offshore, retaining companies in Australia and developing a manufacturing base. “It’s on the radar of both parties, certainly the Industry Department in Canberra is well aware of it and they know what is happening in Europe. As soon as the election is over, we’ll be starting that program in conjunction with other major industry bodies that have manufacturing components.” The second initiative AusBiotech is working on is a position paper to offer more personal tax incentives to people to invest long term in the biotech sector, so-called ‘patient investors in the sector’. “Our sector takes a long time for creation of wealth and we believe there should be personal tax incentives for people who are prepared to put their money into a company and leave it there for a long period of time.” ALS

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AUSBIOTECH | MARKET CHALLENGES

Challenges in the

biotech business Susan Williamson

Establishing a small biotech company and taking products to market are just some of the challenges facing companies in the Australian biotech sector.

t is true, establishing a successful company in the Australian biotechnology sector can take years. A company can take years to emerge from its research base and those investing in this industry need to have patience and money. Setting up and successfully pursuing a small biotech company in Australia is a topic Professor Ian Frazer, CEO and director of research with the Translational Research Institute in Brisbane, has first-hand experience in and is thus well placed to present on at this year’s AusBiotech meeting. Frazer founded the small biotech company Coridon 13 years ago. Coridon’s core focus is a platform technology it uses to develop DNA vaccines for the treatment of a variety of infectious diseases and cancers. And it has just started its first phase clinical trial. Coridon had a good incubation environment at the University of Queensland, although strictly speaking it is not a university spin-off. “The inventors set up the company first,” said Frazer, “then bought the IP from the university. As far as I know, this was a first in Australia. The university has representation on the board but it is not just a university board, which gives the company more flexibility.” Frazer said this model that has worked well because they have university representatives on the board with commercial expertise without the university controlling the company, which enables the company to take more risks. Having this scientific

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and business expertise in the company from the beginning was another thing Frazer said has been key to its success. RAISING CAPITAL

“The reality is that setting up a company in Australia has always been a challenge,” said Frazer, citing two distinct reasons for this. Firstly, attracting or raising enough capital with minimal strings attached, and secondly, manufacturing products for use in human clinical trials. “Venture funds are reluctant to put money into Australian biotech,” he continued. “They drip feed the companies; for some reason they think biotech is not terribly productive in Australia.” One reason for this is that investors want short-term gains when the nature of the life sciences sector is long-term projects. “They want milestones first but we need funding to get the milestones,” said Frazer. “A phase 1 clinical trial takes at least one year of preparation and one year for the trial to be conducted; therefore, you need two years of funding up front.” Frazer added that a lot of good ideas go to the United States. Strong competition from larger rivals in the US as well as a better investor environment mean that a lot of Australian companies take their ideas to the States. According to Frazer, the average phase 1 trial needs funding of about $5 million. “This leap from basic research into the clinic is underfunded in Australia,” Frazer said. “Australia is good at funding basic research but not so good at funding clinical trials.”

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MARKET CHALLENGES | AUSBIOTECH

One key to success is to find an angel investor, which is what Coridon has successfully achieved. “They will provide support and leave you to get on with things.” Coridon’s angel investment has come from Andrew Forrest, a Western Australian mining magnate, through Allied Medical, and before Forrest the Liebermann family. “We also received various government grants,” said Frazer. “But most of the commercialisation schemes are not available any more.” GOOD MANUFACTURING PRACTICE

A new biopharmaceuticals manufacturing plant will be opened in Brisbane in conjunction with the AusBiotech conference. DSM Biologics, in partnership with commercial operator BioPharmaceuticals Australia, has set up a manufacturing facility for biological drug developers. The new facility will provide a manufacturing pathway for early-stage biotherapeutic developers to scale up manufacturing for clinical production and commercial manufacture. Situated next door to the Diamantina Institute, Frazer said the new facility will be very handy in helping him overcome one of the big challenges Coridon has had - manufacturing vaccines to FDA standards. “There has been nowhere in Australia that you could get biopharmaceutical products made to GMP for phase 1 clinical trials up to phase III trials,” he said. “Having DSM next door will be a huge benefit to us in translating our research into the clinic.” INVESTING IN INNOVATION

When it comes to the government, Frazer said innovation should be front and centre on the agenda for the future of Australia. “Biotech is one very successful part of innovation and we need to make sure it remains strong,” he said. “The government needs to pump prime innovation - provide the fuel that lights the fire - then if the fire burns bright the benefits will be reaped later in taxes and so forth.” Investing in basic research and good people is what Frazer says fuels this fire. For innovation to thrive and drive an economy, investment in education is needed to generate the people to do the basic research, in infrastructure to create the spaces where this research can be done, and in innovative research to produce the products and get them to market. “We have been favoured with great infrastructure investment over the last decade, and now we need the ongoing support,” Frazer said. Getting over the initial hurdle of research and development is key to innovation driving the economy and Frazer believes that innovation will always deliver. “We need to encourage venture capitalists in some way, or give superannuation companies the ability to get involved in risky investment,” Frazer said. “Biotech is a long-term investment and superannuation is too, so if we take the same long-term risk for a long-term gain, as long as it is well managed, the industry will benefit.”

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Charles (Charlie) Walker was appointed to the position of Chief Executive Officer in February 2013, following two years as Alchemia’s Chief Financial Officer. He brings 20 years’ international life science industry experience to the role. He originally trained as a pharmacologist in the UK before embarking on a career in the pharmaceutical industry. He subsequently spent more than a decade in corporate finance advising international technology companies, executing more than 40 successful corporate transactions including IPOs, M&A agreements and fundraisings. During this time he co-founded a successful life sciences investment banking firm in the UK which was sold to Nomura International plc in 2005 realising significant returns for investors.

CHALLENGES OF GETTING PRODUCTS TO MARKET

Scott Power, analyst and research writer with stockbroking and wealth management firm RBS Morgans, will chair a session on the challenges of getting products to market at the conference. According to Power, loss of interest has resulted in a downturn in investment over the last five years in the Australian life sciences sector. “Apart from the risk appetite disappearing as people become more cautious, we’ve also got the failure of companies to get their products approved,” said Power, although he thinks things have turned around a bit in the last couple of months. INVALUABLE APPROVAL

Failing to get products approved means companies lose money. Delays in approval prevent products from being progressed, putting downward pressure on share prices, which in turn puts investors off. On top of this, companies then spend more money to employ consultants, advisors and/or lawyers to continue negotiations with regulators. Getting approval from regulators is one of the main challenges Power identified for biotech companies developing a product or medical device. “What we are finding is that once products are approved they are worth their weight in gold. An approved product in a market that is growing is extremely valuable,” said Power. Companies can work tirelessly on clinical trials to get results for their products only to fail the scrutiny of the regulatory regimes - the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Power said he has seen a number of products that should have been approved fall foul of the regulators over the last few years. “In some instances it doesn’t seem to correlate well with common sense,” he said.

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AUSBIOTECH | MARKET CHALLENGES

One example Power cited was Tissue Therapies, which has been working towards getting its wound-healing product, VitroGro, onto the European market. “The company basically lost six to nine months through the approval process, for reasons which I cannot explain, and neither can they,” said Power. “Their application to get the product approved was delayed but they are very much back on schedule with an expected approval date of the second quarter next year.” As this issue of ALS went to print, Tissue Therapies had received confirmation from the EMA that the final step in the process of getting VitroGro to the European market would start at the beginning of September - and their share price was heading up.

Scott Power is a senior research analyst with RBS Morgans. Based in Brisbane, he completed a Bachelor of Commerce, Accounting and Finance at the University of Queensland in 1983 and since then has worked as an investment manager with the Queensland Industry Development Corporation and as an analyst with RBS Morgans. He has continually focused his work on the analysis and research of emerging technologies and early-stage businesses in the life science sector.

THE APPROVAL PROJECT

Alchemia CEO Charles Walker, who will present in the Challenges of Getting Products to Market session at the conference, concurs. “It’s a huge project all on its own,” Walker said of the approval process. “They [the regulators] want to see everything, all your scientific data - there is lots of toing and froing.” Walker said making early contact with the FDA and building a relationship with it was an important part of this process, which is something Alchemia has embarked on with its chemotherapy drug HA-Irinotecan. “We’ve been to the FDA and flagged what we are doing. They have to know who you are and the clinical trial that you are conducting,” he said. “We’ve gone to Europe [the EMA] at the same time, we’re trying to get a submission package that works for both of them - that would be an ideal outcome. There’s always going to be differences but the indications are good so far.” HA-Irinotecan is currently in a phase III trial in patients with metastatic colorectal cancer. Walker said the results are expected in the first half of 2014 and, all going well, they will file with the FDA the same year and get it approved for launch in 2015.

Professor Ian Frazer trained as a renal physician and clinical immunologist in Edinburgh, Scotland, before moving to Australia to pursue a research career in viral immunology and autoimmunity at the Walter and Eliza Hall Institute of Medical Research in Melbourne. He took up a teaching post at the University of Queensland in 1985 and is now group leader at the Diamantina Institute and CEO and director of research at the Translational Research Institute. Frazer is also a director of biotech company Coridon.

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Another company, Sydney-based QrXPharma, recently resubmitted an application to the US FDA for its pain patch MoxDuo - having had its initial application knocked back in June 2012. “They provided compelling clinical data on this product to treat acute pain,” said Power, “and are currently still trying to get approval after receiving a Complete Response letter from the FDA, which essentially required them to collate some more data to build up their case.” QrX Pharma’s original plan was to have MoxDuo approved in July this year. “In fact, the product would be on the market today so they would be generating sales,” Power continued. “As it stands we are hoping the product will be approved sometime in November, so effectively they’ve lost six months’ worth of sales.” QrX Parma’s share price had climbed back to $1.13, after dropping from $1.60 to below $1 when they reported the delay in getting MoxDuo to market. PARTNERING

Manufacturing and marketing are other challenges Walker raised in getting products to market, and for him this involves partnering. “Depending on what the product is, most biotech companies have probably got to rely on a partner - it’s just a question of when,” said Walker, who joined Alchemia just as its generic antithrombotic drug Fondaparinux received approval 2.5 years ago. “Knowing our strengths in that situation was the key,” Walker explained. “Typically, biotechs are good on the innovation, which is a completely different skill from commercialisation. I think practically for biotechs, partnerships make a lot of sense to achieve that.” Partnering means companies could lose some of the value of the product but Walker said tapping into the expertise of others is worthwhile. “Optimal commercialisation with an experienced partner could more than compensate a biotech for striking a deal with that partner,

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MARKET CHALLENGES | AUSBIOTECH

when the risk of sub-optimal commercialisation is evaluated,” he said. “We could raise funds, invest heavily after the results, recruit a new commercialisation team and take our products all the way through and market them, but the risk is we would risk losing focus on our core capability of R&D, and not make the most of the product when it comes to marketing and sales. "Licensing the product to another company in return for their expertise and presence in our target market can be a good thing because it means we can be more sure of optimal commercialisation and maximal profits down stream.” Walker said the partnership with India-based manufacturing specialist Dr Reddy’s Laboratories was going well, with Fondaparinux selling in the US and Alchemia receiving a profit share from those activities. OUTSOURCING

Most biotech companies outsource steps along the way, such as manufacturing - scaling up from a clinical trial is a huge task. Sydney-based pharmaceutical company Pharmaxis made the brave decision to take its product bronchitol to market. “Pharmaxis was one of the premier stocks in the sector a few years ago,” said Power, adding that Pharmaxis has had

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a series of setbacks that have led to its share price dropping significantly. “They took the view that they would discover, manufacture and sell their product [bronchitol], and that strategy has failed.” Power also suggested the difficulties Pharmaxis had in dealing with regulators has had a big effect on where the company is now at. At this stage, Alchemia contracts out the manufacturing side of its process. “We’ve got the brains and we use someone else’s hands,” Walker said. “You’ve got to have your manufacturing organised, you’ve got to have people of influence - buyer and payers in the market - and all of that we’re choosing to get from third parties. As our company develops more products that are successfully launched, and we grow our expertise in the area, we may then consider commercialising products ourselves.” Walker said outsourcing is an efficient way to do things business wise and the selection of good quality contract manufacturers available makes it a relatively easy decision. “Raising money, getting good people, developing good trial designs - that’s all part of the challenges that companies face in this sector,” he added. ALS

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Personalised

medicine

Susan Williamson

The investment that has been put into personalised medicine is starting to pay off - the tailored diagnosis, prognosis, treatment and prevention of disease in an individual is beginning to be applied, as David Randerson intends to explain at the conference.

efining treatment through an individuals’ genetic and phenotypic information promises better management of diseases that will bring benefits to the economy, society and people’s quality of life. According to David Randerson, Chief Executive Officer and Managing Director of TransBio and the Cooperative Research Centre (CRC) for Biomarker Translation, one of the big drivers of personalised medicine is the cost of healthcare delivery. “Personalised medicine is important from an economics point of view because the cost of treating patients is becoming prohibitively expensive,” said Randerson, who will open the personalised medicine session at the conference. “For example, there is a new cystic fibrosis drug on the market that costs $300,000 a year,” he said of the medication Kalydeco, which was recently approved for use in Australia.

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Patients with cystic fibrosis who have the G551D mutation are eligible for this treatment. Other specific cancer drugs, such as the prostate cancer immunotherapy Provenge, costs up to $100,000 for a course of treatment, and ongoing biological treatments for rheumatoid arthritis cost between $13,000 and $30,000 for a course. Because new drugs coming onto the market are getting more and more expensive, identifying whether a patient will respond or fail or develop adverse effects is key to appropriately directing national health and insurance costs. Giving the same treatment to every patient with a particular disease is not economical because many of these patients will not respond to the treatment. It also increases the potential of serious side effects developing. “As drugs become more targeted the potential to develop serious side effects become greater,” Randerson explained.

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“So if you can identify patients who will respond to a particular treatment, you are treating them with the knowledge that the drug will be effective.” PREVENTATIVE MEDICINE

Personalised medicine is also important from a preventative perspective, which links to the expense of healthcare. Biomarkers, genetic markers or proteomics can be used to identify and monitor people who are predisposed to getting a particular disease. They can then be encouraged to modify their lifestyle or be treated before they progress into that condition. “It may be arthritis or Alzheimer’s disease, then you can pre-empt that disease, treat people and treat them cost effectively,” Randerson said. “Whereas treating patients who are not going to respond to the treatment is a waste of time and money.” According to Randerson, Australia is particularly good at this preventative approach, as is Europe.

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One of the early targeted therapies identified was the monoclonal antibody Herceptin. A relatively large subgroup (25%) of patients with breast cancer - those with human epidermal growth factor receptor HER2-positive breast cancer responded to the targeted treatment. “It may be that 25% of breast cancer patients are amenable to herceptin but, in reality, you go through and select those patients as part of your clinical trial,” explained Randerson. “We are doing this right now with some of the work at the CRC. We look at where a particular drug will be effective, which patients are most amenable to the drug, then we identify those patients by a test, using a biomarker for example, and then go into a trial. Otherwise we are not going to be able to get statistical significance.”

David Randerson is Chief Executive and Director at TransBio Ltd and the Cooperative Research Centre for Biomarker Translation and Managing Director at Acuity Technology Management. He studied his undergraduate at Monash University and completed a PhD in Biomedical Engineering at UNSW. He has worked as a research scientist in academia and industry. His current focus is on providing advice on R&D and commercialisation in the healthcare and biotechnology sector.

COMPANION DIAGNOSTICS

Coupling a diagnostic test with a drug is beneficial from a number of perspectives. From a company’s perspective, aligning a diagnostic test with a particular therapy may give them greater protection from a patent point of view. “It enables companies to verify that their drugs are effective in a particular subset of patients,” said Randerson. “This gives them a stronger market presence.” From an individual’s perspective, it enables clinicians to determine which drug is going to work best for a person with minimal side effects. It also prevents a potentially good drug from being rejected because it has no or minimal effect in the whole patient population. Randerson believes that many potential new drugs that may have worked in 1, 5 or 20 per cent of a patient population have been lost over the years because their effects did not appear in the data. The FDA has already approved at least four drugs, and Europe has approved 11, that require a specific concomitant diagnostic test to be conducted. The test identifies whether the patient is part of a particular subset of that disease and is therefore likely to respond to the treatment. Randerson predicts that this type of testing will become more and more common as personalised medicine gains ground in the future.

S E P T E M B E R / O C TO B E R 2 013

“It is a much more targeted groups of patients that these therapies are being developed for, and this is changing the way things are done,” he said. THE END OF A TERM

One project currently underway within the CRC for Biomarker Translation involves a program for developing specific markers to detect T helper cells Th1 and Th17 cells. Th1 and Th17 cells are involved in the inflammatory process in rheumatoid arthritis and the work, conducted at the Burnett Institute in Melbourne, has identified a number of specific markers for these cells. Randerson predicts there may be a therapeutic interest in these cells in the future but, with only a year remaining of its seven-year term, the CRC does not have time to pursue this pathway. Instead the focus is on developing a guiding tool or diagnostic for treatment with a focus on rheumatoid arthritis. The treatments available for patients with rheumatoid arthritis all have a significant rate of failure. A specific population of Th17 cells is present in some patients who respond

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to a specific therapy. By monitoring the Th17 cells, or specific subsets of T cells, in these patients, the researchers hope to be able to predict those patients who will respond to a particular treatment. “We look in the synovial fluid taken from patient’s joints and can demonstrate there’s a subset of Th17s which are identifiable by a specific marker,” said Randerson. “These can be used to guide therapy and will produce better outcomes for patients with fewer side effects and less waste.” Randerson hopes that over the next 12 months the team will be collaborating with a major drug company to finalise some of the work that has come out of the CRC before its term ends in July 2014. “We’ve identified several hundred biomarkers and then developed or used commercially available monoclonal antibodies to validate those biomarkers,” Randerson reflected. Randerson said the CRC has narrowed its work down five or six projects and is hopeful that over the next 12 months the projects will attract licences or investment. ALS

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BIOTECH NEWS | ROUND UP

CSL boosts FY13 profit by 19% CSL (ASX:CSL) has reported a 19% increase in FY13 profit to US$1.21 billion ($1.33 billion), despite exchange rate losses taking a bite out of both profit and revenue. Excluding a US$18 million forex impact, net profit would have grown 21% in constant currency. Sales for the quarter increased 7% to US$5 billion, but were up 10% at constant currency. CSL attributed the higher revenue to strong sales growth in its immunoglobulin, albumin and specialty product segments. Sales at plasma division CSL Behring increased 10% to US$4.5 billion. “The company’s core products of immunoglobulin and albumin have performed very well and we have strengthened our margins through a change in sales mix and a relentless pursuit of efficiency,” CSL CEO Paul Perrault said. “Our suite of specialty products [also] grew strongly, supported by the registration in the US of Kcentra, a product used in the urgent reversal of anticoagulant warfarin in patients with acute major bleeding.” Revenue from bioCSL meanwhile grew 8% in constant currency, but influenza sales declined due to global influenza

Dylan Bushell-Embling market dynamics and the Australian operating environment. Despite ongoing economic pressures, the company is forecasting profit growth of around 10% at constant currency for FY14. CSL also announced two changes to its board, including the immediate appointment of a new director. Marie McDonald, a partner of Ashurst and chair of the Corporations Committee of the Business Law Section of the Law Council of Australia,

has joined the board. McDonald has a strong background in corporate and commercial law. She has also served as a member of the Australian Takeovers Panel from 2001 to 2010. Long-serving director Ian Renard announced his decision to retire from the board. Renard has been a director of the company since 1998. He has been a member of the company’s audit and risk management committee since the year he started and chair of the committee since 2008. Before becoming a CSL director, he advised the board on its privatisation and ASX listing in 1994, under his capacity at the time as a partner of Arthur Robinson & Hedderwicks.

Industry invests in university Chair A new industry-sponsored Chair at The Australian National University (ANU), which will focus on research into localised cancer treatment, will see Sirtex Medical (ASX: SRX) commit up to $3m over three years to the position. The Sirtex Chair will be held by Professor Ross Stephens, from the Department of Applied Mathematics, and the funding will support research conducted at the department led by Professor Stephens and Professor Tim Senden, Head of the Department. The research will focus on new adaptions of Sirtex’s existing technology - a targeted radiation therapy for patients with inoperable liver cancer. The aim is to create a biomedical technology that will stop the collateral

S E P T E M B E R / O C TO B E R 2 013

damage of healthy cells in cancer patients by localising the radiation treatment at tumour sites. “We’re trying to fashion an internal therapy that is highly localised and that also gives doctors flexibility in designing individual treatment plans.” Professor Senden said that the Chair and its associated funding would enable a significant push in research that could have real potential for applications in areas of unmet medical need. Profits exceed expectations Sirtex's FY13 profits came in ahead of expectations. The company reported a total revenue of $100.3 million, an increase of 16% on the previous financial year, and a net profit after tax of $18.3 million, up 7% on last year.

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Sirtex has been one of the bestperforming stocks on the ASX during the last financial year, with its share price doubling from around $6 to $12. This rise is thanks to strong dose sales of Sirtex’s SIR-Spheres, a targeted radioactive liver cancer treatment. The largest growth was in the US, where sales rose by 21.4%. Across Europe, the Middle East and Africa (EMEA), sales were up 9% and in the AsiaPacific doses increased by 29.5%. With work on a new manufacturing facility in Germany progressing to schedule, sales in Europe should continue to grow. Sirtex has also invested $15.8 million into its global clinical program, which aims to make its targeted radiation therapy a firstline treatment option for patients with liver cancer.

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BIOTECH NEWS | ROUND UP

Dr Rathjen elected

Dr Deborah Rathjen, Managing Director of Bionomics and Chair of AusBiotech, has been elected as the Chair of the Pharmaceuticals Industry Council (PIC). Dr Rathjen will hold this position until at least June 2014. Dr Rathjen said she is delighted to be named the PIC’s Chair. “The Australian biopharmaceuticals industry faces many serious challenges, such as the constant danger of further price cuts, a declining number of clinical trials conducted in this country, a shortage of incentives to support the growth of Australia’s medical biotechnology sector and a complete lack of globally competitive incentives to encourage manufacturing investment in Australia. “Even so, with the rise of Asia, we have an incredible opportunity to position Australia as a regional biopharmaceutical manufacturing and R&D hub,” Dr Rathjen said. “Australia boasts some of the world’s best scientists and research infrastructure. And we are world renowned for manufacturing medicines and vaccines of the very best quality. “To capitalise on this unique opportunity, we need well-designed policies that encourage the full spectrum of activities in this high-value industry, from basic R&D to full-scale manufacturing.” Dr Rathjen also paid tribute to her predecessor, Dr Martin Cross, who stepped down from the position in June. “I want to thank Martin for his leadership of the PIC over the past 18 months. He is an exceptional advocate for the industry, and we will miss his enthusiasm and remarkable advocacy skills.” Dr Rathjen said that she looks forward to working with fellow PIC members, the Australian Government and other stakeholders to ensure a positive operating environment for the Australian biopharmaceuticals industry. About the PIC Since 2006, the Pharmaceuticals Industry Council has been a forum for developing, evaluating and providing expert advice to government on issues affecting the Australian pharmaceuticals industry. It brings together senior executives from companies and peak bodies representing three industry sectors, including the research-based and generic medicines sectors and the biotechnology sector. Collectively, these three sectors employ in excess of 40,000 highly skilled Australians, export over $4 billion worth of medicines annually and invest more than $1 billion per year in research and development collaborations with local hospitals, universities and research organisations. The industry is a major innovative contributor to the economy and one of the most R&D intensive industries in Australia.

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AU S T R A L I A N L I F E S C I E N T I S T

Pharmaceuticals Industry Council Chair ResMed FY13 profit grows 21%

ResMed (ASX:RMD) grew its FY13 profit by 21% to US$307.1 million ($345 million), from 11% higher revenue of US$1.5 billion. Profit for the year was impacted by ResMed’s recent $25 million payment to the University of Sydney to settle a licensing dispute and support joint research into sleep-disordered breathing. Excluding this one-off charge, net profit would have grown 27.5% to US$324.8 million. The payment was also responsible for a 5% decline in reported Q4 profit to US$73 million. Fourth quarter revenue increased 11% to a record US$414.6 million. ResMed CEO Mick Farrell attributed the result to solid sales growth across its key sales regions. “Revenue in the Americas increased by 11% over the prior year’s quarter to $230.3 million for Q4. Revenue in Europe and Asia-Pac combined reached $184.3 million, an increase of 12% [year on year],” he said. R&D costs for Q4 grew 12% to US$31.4 million. Without the recent depreciation of the Australian dollar, these costs would have risen by 14%. ResMed launched several new products during the quarter, including a home variable positive airway pressure (VPAP) device for chronic obstructive pulmonary disease, as well as an online and mobile app to track sleep-disordered breathing treatment progress.

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BIOTECH NEWS | IMMUNOTHERAPY

cancer

immunotherapy trials Dylan Bushell-Embling

The life science sector is devoting a lot of attention to immunotherapy in cancer treatment. Citi Research Equities recently estimated that immunotherapy will become the treatment backbone for up to 60% of cancers over the next 10 years.

elbourne-based Ascend Biopharmaceuticals is preparing to enter pivotal clinical trials for two cancer treatment candidates, a cancer vaccine and a virus, and is well placed to capitalise on this immunotherapy momentum. Ascend CEO Clement Leong said the Australian trials will focus on breast cancer and nodular basal cell carcinoma (BCC). Ascend Biopharmaceuticals was founded out of Australia’s Austin Research Institute - now the Burnet Institute - in 2006. Leong was a founding investor and chairman of the company, and was appointed CEO around a year ago. ASN-004: TRAINING THE IMMUNE SYSTEM

ASN-004 is a cancer vaccine which is designed to train the immune system to selectively destroy cancer cells by recognising tumour antigen MUC-1. The antigen is expressed in a wide variety of cancer types, but Ascend is initially planning to commercialise the vaccine in breast cancer. Leong said the breast cancer focus is due to the development history of the product. The vaccine is based on work by then Austin Research Institute Professor Ian McKenzie during the late ’80s and early ’90s. The work culminated in a study demonstrating encouraging results in early-stage breast cancer. “When we saw the data we were very impressed,” Leong said. “We knew that we had to do a lot of work around moving what was an academic program into a bona fide commercial program, but there were sufficient tantalising clinical results in breast cancer that caused us to invest into the program.” During the course of clinical development, which focused on ensuring the product is approvable by regulators, the company has discovered ways to make improvements to the original composition. “We were able to discover that there’s a way of improving the immunogenicity of the vaccine,” Leong said. While the details are subject to change, Ascend plans to commence a phase Ib trial of ASN-004 in late 2014. The company

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aims to enrol 24 breast cancer patients. Leong said the company felt the need to go back to a phase Ib study because of the improvements made to the vaccine composition. “We’re building a bridge with a new product that we believe will be acceptable to the regulators,” he said. “And that’s why we really need to [re-establish] basic safety and basic characteristics of the product.” ASN-002: AN EASIER PATH TO MARKET

ASN-002 is a virus designed to kill cancer cells through the release of interferon into tumour cells. Ascend has in-licensed the virus from French pharmaceutical company TransGene, and finally consummated this deal in June. Ascend plans to trial the virus in BCC this year. Ascend has already identified three clinical sites and is engaging with new contract manufacturers capable of growing with the company. TransGene had originally studied the virus in cutaneous lymphoma and achieved good clinical results showing that the composition is well tolerated, so the company is looking at conducting a phase IIa study. The choice of BCC as a target provides some key benefits for Ascend. For starters, BCC is very prevalent in Australia, meaning the company will have a large pool of patients to draw from. From a regulatory perspective, the barrier to approval is also lower, at least in the US, Leong said. The FDA typically uses overall survival time as the clinical measure for approving a cancer treatment, which can take 3-5 years to demonstrate in a trial. But for BCC products, regulators use a metric called histological clearance. “You treat the cancer and you go back at the end of treatment and do a biopsy, and if there’s no more histological evidence of the cancer cell in the biopsy then it’s viewed as having cleared,” Leong said. “By virtue of that end point, one can potentially complete a clinical trial in a third of the time or even less [compared to] an overall survival study.” ALS

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The high-voltage power supply results in a fast maximum scan rate of 30,000 Âľ/s and 5 ms polarity switching time. In addition, it is now possible to include 1000 events with up to 32 channels per event for a maximum of 32,000 MRMs per analysis. Shimadzu Scientific Instruments (Oceania) Pty Ltd Contact info and more items like this at wf.net.au/U886

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Automated colony counter Synbiosis has introduced its aCOLyte 3 colony counting system, which is suitable for microbiologists who need to significantly increase their throughput and improve count accuracy. The automated colony counter is designed for a rapid count of pour, spread and spiral plates. The system can read plates of up to 90 mm in seconds, generating precise plate count results up to 10 times faster than manual counts. The numerical count data and plate images can be directly transferred to Excel or OpenOffice to avoid errors in data transfer, ensuring accurate GLP-compliant result reporting and archiving every time. The product provides full colour image display and comes complete with software based on Synbiosisâ&#x20AC;&#x2122; powerful ProtoCOL 3 software. The system can be supplied with a computer or scientists can use their own laptop or desktop PC and simply connect the device via a USB port. The unit is lit by white LEDs mounted above and below the plate, enabling accurate detection of colonies as small as 0.3 mm. For laboratories where strong ambient light could interfere, there is also the option to have a detachable screen fitted to prevent any reflection or glare affecting the count. Don Whitley Scientific Pty Limited Contact info and more items like this at wf.net.au/U012

15 mL centrifuge tube The Cellstar CELLreactor from Greiner Bio-One is a 15 mL polypropylene centrifuge tube with a 0.2 Âľ PTFE membrane contained within the screw cap to facilitate cell growth while still providing a sterile environment. The tube can be used as a small bioreactor to cultivate suspension cells. It can also be used for the culture of aerobic bacteria, yeasts and other microorganisms. Suitable for work with spheroids, there is no need for transfer of cells for harvest as they can be centrifuged directly in the tube. 50 mL tubes are also available. Interpath Services Pty Ltd Contact info and more items like this at wf.net.au/U891

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Pertussis toxin Pertussis toxin (PT), a virulence factor produced by Bordetella pertussis, is a multisubunit toxin which binds to most cultured mammalian cells and targets specific G protein, inhibiting the ability of the G protein to function in signalling pathways. Depending on the function of the G protein, the effects of PT can vary.Â This ability to inhibit pathways using the Gi family of protein-coupled receptors is the basis of the use of PT as a tool in cell biology. PT plays a role in infection by sup-

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Parallel evaporation system Scitek introduces the Genevac miVac series rotational vacuum concentration system, which has been specifically designed for fast yet gentle parallel low-temperature water and solvent removal. The miVac DNA is a small vacuum concentrator for the molecular biology laboratory. It is capable of removing water and organic solvents from a variety of sample formats including microtubes, centrifuge tubes, microplates, vials and round bottom flasks, making it a suitable concentrator for the busy molecular biology laboratory. The miVac Duo and Quattro are higher capacity concentrators suitable for even busier users. miVac concentrators are very quiet. The design includes a system preheat function, said to result in process times up to 40% faster than comparable machines. Pre-programmed methods for water, solvents and maximum performance make usage very straightforward. The miVac Speedtrap allows for significant improvement of process times and enables lyophilisation (freeze drying) in one system. Vacuum pump options include two corrosion-resistant diaphragm pumps and a scroll-type, high-performance pump capable of freeze drying samples. Scitek Australia Pty Ltd Contact info and more items like this at wf.net.au/U580

Tacky mats The VWR PureStep multi-layered, adhesive-coated mat removes dirt and dust from foot traffic and wheels prior to entry into a critical manufacturing environment. A consistent coat weight of adhesive produces a higher-performing mat without excessive tack issues. The mats are produced in an ISO 9000 factory with QC test data and reports available for each case. Each layer is fully coated with a particle-grabbing adhesive and constructed of 1.8 m/45 Âľm lowdensity polyethylene film. The mats can be applied directly to the floor or used with frames where direct adhesion is not possible. The mats are available in 30 or 60 layers, in multiples sizes with various frame options. They feature low-profile, numbered tabs indicating remaining layers and that only one layer is removed at any time. The consistent adhesive coverage ensures maximum performance of each layer. VWR International Pty Ltd Contact info and more items like this at wf.net.au/T705

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MALS detector for size-exclusion chromatography The Viscotek SEC MALS 20 is an advanced multi-angle light scattering (MALS) detector for size-exclusion chromatography (SEC/GPC). It is used to measure absolute molecular weight of proteins, synthetic and natural polymers. In conjunction with a concentration detector, molecular size (expressed as the radius of gyration) can also be determined. For proteins, the product measures the absolute molecular weight independent of column retention volume in order to study oligomeric

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solvents. Malvernâ&#x20AC;&#x2122;s static light-scattering detectors, including low-angle (LALS), right-angle (RALS) and multi-angle (MALS), are available individually and are compatible with any commercial GPC/SEC system, or may be supplied integrated within a multi-detection Viscotek system for comprehensive polymer, protein and macromolecule characterisation. ATA Scientific Pty Ltd Contact info and more items like this at wf.net.au/U905

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Nucleic acid molecule detection system The NanoString nCounter Analysis System uses fluorescent barcodes to detect and count single nucleic acid molecules by direct hybridisation and can be multiplexed for up to 800 different targets in a sample. This high level of multiplexing and pure digital detection avoids the pitfalls of enzymatic steps such as reverse transcription and PCR while offering high precision and reproducibility. In addition, NanoString technology is amenable to challenging sample types such as formalin-fixed, paraffinembedded (FFPE) tissue, cell lysates and raw biofluids. An expanding list of applications includes gene expression, singlecell gene expression, miRNA expression and fusion gene analysis. DNA applications include copy number variation (CNV), ChIP and haplotyping. The technology is a suitable choice for validation studies and translational research applications. It offers the three key characteristics required to accelerate genomic discoveries into robust clinical assays: mid- to high-multiplexing capacity capturing the key findings of NGS discovery; digital readout for direct comparison with NGS; and an automated, enzymefree workflow for fast and accurate quantitation of thousands of samples in retrospective-prospective studies using FFPE samples. Key benefits include: no amplification (except for single-cell assays), RT or sample partitioning; digital counting of single molecules for low noise data; reproducible with wide dynamic range and high precision; expression calls in 10 min (no compute clusters); simple workflow - up to 800 targets in a single tube. Bio-Strategy Pty Ltd Contact info and more items like this at wf.net.au/U675

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Programmable refrigerated circulating baths A line of sophisticated circulating water baths that make it simple to create and run multistep ramp and soak temperature programs, as well as frequently used single temperature testing protocols, is now available from PolyScience. Designed with the work habits and the needs of laboratory personnel in mind, PolyScience Advanced Programmable Circulating Baths feature an icon-driven, touch-screen display that makes selecting and setting operational parameters simple and straightforward. A built-in electronic keypad speeds up and simplifies the entry of text and numerical values. Available in both refrigerating/heating and heat-only models, the units control bath temperatures as broad as -40 to +200°C with ±0.01°C stability. Highly customisable, they feature a variety of user-settable operational parameters, including the size, style and type of temperature information that is displayed as well as the menu/display language. Other lab-friendly features include a rotating control head that provides a clear view of the temperature display anywhere within a 180° viewing radius; variable-speed suction/pressure pump suitable for closed and open-loop external circulation; remote temperature sensing capability; and serial, USB and ethernet communications. The baths are available in reservoir sizes ranging from 7 to 45 L. A 75 L unit is also available for beer and beverage testing. Bioline Global Pty Ltd Contact info and more items like this at wf.net.au/U819

Climate chamber Generation 2012 climate chambers from Memmert offer features to enhance the productivity of the laboratory. The chambers are energy efficient and have a long, maintenance-free service life, making them suitable for stability tests, environmental conditioning, storage and quality assurance testing. Offering high-precision temperature control from 0 to 70°C, active humidification and dehumidification from 10 to 90% relative humidity and light modules for warm or cold white light, the units provide options for multiple applications. The appliances use Peltier technology, which results in the range heating and cooling without vibration or noise. Because it runs so quietly, the constant climate chamber is suitable not only for environment simulation and long-term material tests but also for breeding insects and reptiles. Energy consumption can be reduced by up to 90% when compared to compressor technology and Peltier technology requires no coolants or regular maintenance. Additional features include ethernet connectivity, AtmoControl software and full IQ/OQ/PQ documentation is available. In Vitro Technologies Pty Ltd Contact info and more items like this at wf.net.au/U016

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CO2 incubators

New Brunswick’s Galaxy CO2 incubators, available from Eppendorf, provide a suitable environment for a wide range of culture applications like stem cell research, oncology, IVF, anaerobic bacterial growth, neuroscience, viral studies and more. The incubator has a fanless, seamless chamber, with options for high-temperature disinfection and a copper interior providing good contamination control. Three O2 control options enable specialised high- and low-oxygen applications. The 14 L incubator fits under a hood, so it’s suitable for isolating critical cultures, ensuring assay validity. Offered in advanced and economical models, in a range of three sizes (14-170 L), the directheat systems expand the user’s cell culture possibilities. Eppendorf can offer a tailored CO2 incubator that is both robust and highly controllable to play an integral role in the laboratory. Eppendorf South Pacific Pty Ltd Contact info and more items like this at wf.net.au/U510

Laboratory sample management system Track-IT is a laboratory sample management system (LSMS) that allows fast and efficient management of all samples and reagents within the laboratory. Web-based access allows each scientist in the lab to access and manage laboratory sample data and information quickly while making it available to the rest of the lab community. Designed with the end user in mind and built around independent modules that can interact with each other, the product will manage a variety of day-to-day useful lab information. A simple-to-use graphical interface means that no informatics skills are required and the LIMS database can be used immediately by all laboratory staff without complex configurations or long learning phases. The system allows the user to: organise all laboratory samples, cell lines, plasmids, primers and antibodies; record chemical compound and structures; control documents, protocols, SOPs and MSDSs; manage sequencing and microarray data; monitor reagent stock level and expiry dates; maintain equipment warranties and maintenance schedules. Fully compatible with barcode scanning, the product allows the generation of 1D and 2D barcodes and the cataloguing of samples and reagents that have been scanned by lab equipment, such as barcode readers and scanners. Complete user customisation of the database’s modules and data fields allows the database to match the workflow of the laboratory and the aspects of each sample. In Vitro Technologies Pty Ltd Contact info and more items like this at wf.net.au/U772

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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. Ariotti N, Parton RG. SnapShot: Caveolae, Caveolins, and Cavins. UQ Snapshot: caveolae, caveolins, and cavins.

Cell. 2013 Aug 1;154(3):704-704.

Avdic S, Cao JZ, McSharry BP, Clancy LE, Brown R, Steain M, Gottlieb DJ, Abendroth A, Slobedman B. Westmd Millen Inst Human cytomegalovirus interleukin-10 polarizes monocytes toward a deactivated M2c phenotype to repress host immune responses.

J Virol. 2013 Sep;87(18):10273-82.

Beavis PA, Divisekera U, Paget C, Chow MT, John LB, Devaud C, Dwyer K, Stagg J, Smyth MJ, Darcy PK. Peter Mac Blockade of A2A receptors potently suppresses the metastasis of CD73+ tumors.

Proc Natl Acad Sci USA. 2013 Aug 20.

Beck D, Thoms JA, Perera D, Schütte J, Unnikrishnan A, Knezevic K, Kinston SJ, Wilson NK, O’Brien TA, Göttgens B, Wong JW, Pimanda JE. UNSW Genome-wide analysis of transcriptional regulators in human HSPCs reveals a densely interconnected network of coding and noncoding genes.

Blood. 2013 Aug 23.

Bekkers JM, Suzuki N. JCSMR ANU Neurons and circuits for odour processing in the piriform cortex.

Trends Neurosci. 2013 Jul;36(7):429-38.

Bell-Anderson KS, Funnell AP, Williams H, Mat Jusoh H, Scully T, Lim WF, Burdach JG, Mak KS, Knights AJ, Hoy AJ, Nicholas HR, Sainsbury A, Turner N, Pearson RC, Crossley M. USyd Loss of kruppel-like factor 3 (KLF3/BKLF) leads to upregulation of the insulin-sensitizing factor adipolin (FAM132A/CTRP12/C1qdc2).

Diabetes. 2013 Aug;62(8):2728-37.

Bieri FA, Gray DJ, Williams GM, Raso G, Li YS, Yuan L, He Y, Li RS, Guo FY, Li SM, McManus DP QIMR, UQ Health-education package to prevent worm infections in Chinese schoolchildren.

NEJM. 2013;368:1603-12.

Goldsworthy MR, Vallence AM. Univ Adel The role of β-amyloid in Alzheimer’s diseaserelated neurodegeneration.

J Neurosci. 2013 Aug 7;33(32):12910-1.

Groszmann M, Greaves IK, Fujimoto R, James Peacock W, Dennis ES. CSIRO Plant Ind The role of epigenetics in hybrid vigour.

Trends Genet. 2013 Aug 14.

Haroon MF, Hu S, Shi Y, Imelfort M, Keller J, Hugenholtz P, Yuan Z, Tyson GW. UQ Anaerobic oxidation of methane coupled to nitrate reduction in a novel archaeal lineage.

Nature. 2013 Jul 28.

Hocking S, Samocha-Bonet D, Milner KL, Greenfield JR, Chisholm DJ. Garvan Adiposity and insulin resistance in humans: the role of the different tissue and cellular lipid depots.

Endocr Rev. 2013 Aug;34(4):463-500.

Huang C, Shen S, Ma Q, Chen J, Gill A, Pollock CA, Chen XM. RNS Hosp, USyd Blockade of KCa3.1 ameliorates renal fibrosis through the TGF-β1/Smad pathway in diabetic mice.

Diabetes. 2013 Aug;62(8):2923-34.

Johnson TK, Crossman T, Foote KA, Henstridge MA, Saligari MJ, Forbes Beadle L, Herr A, Whisstock JC, Warr CG. Monash Uni Torso-like functions independently of Torso to regulate Drosophila growth and developmental timing.

Proc Natl Acad Sci USA. 2013 Aug 19.

Johnston SE, Gratten J, Berenos C, Pilkington JG, Clutton-Brock TH, Pemberton JM, Slate J Qld Brain Inst UQ Life history trade-offs at a single locus maintain sexually selected genetic variation.

Nature. 2013 Aug 21.

Kershaw MH, Smyth MJ. Uni Melb Immunology. Making macrophages eat cancer.

Boddey JA, Cowman AF. WEHI, Uni Melb Plasmodium nesting: remaking the erythrocyte from the inside out.

Science. 2013 Jul 5;341(6141):41-2.

Chow Z, Mueller SN, Deane JA, Hickey MJ. Monash Med Cntr Dermal regulatory t cells display distinct migratory behavior that is modulated during adaptive and innate inflammation.

Trends Biochem Sci. 2013 Jul;38(7):350-5.

Annu Rev Microbiol. 2013 Jun 26.

J Immunol. 2013 Aug 12.

Dugdale B, Mortimer CL, Kato M, James TA, Harding RM, Dale JL. QUT In plant activation: an inducible, hyperexpression platform for recombinant protein production in plants.

Plant Cell. 2013 Jul;25(7):2429-43.

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Lott WB, Doran MR. QUT Do RNA viruses require genome cyclisation for replication?

Maña P, Liñares D, Silva DG, Fordham S, Scheu S, Pfeffer K, Staykova M, Bertram EM. JCSMR ANU LIGHT (TNFSF14/CD258) is a decisive factor for recovery from experimental autoimmune encephalomyelitis.

J Immunol. 2013 Jul 1;191(1):154-63.

Moon H, Lee CS, Inder KL, Sharma S, Choi E, Black DM, Lê Cao KA, Winterford C, Coward JI, Ling MT; the Australian Prostate Cancer BioResource, Craik DJ, Parton RG, Russell PJ, Hill MM. UQ Diamantina Inst PTRF/cavin-1 neutralizes non-caveolar caveolin1microdomains in prostate cancer.

Oncogene. 2013 Aug 12.

Moritz C, Agudo R. ANU The future of species under climate change: resilience or decline?

Science. 2013 Aug 2;341(6145):504-8.

Periyannan S, Moore J, Ayliffe M, Bansal U, Wang X, Huang L, Deal K, Luo M, Kong X, Bariana H, Mago R, McIntosh R, Dodds P, Dvorak J, Lagudah E. CSIRO Plant Ind The gene Sr33, an ortholog of barley Mla genes, encodes resistance to wheat stem rust race Ug99.

Science. 2013 Aug 16;341(6147):786-8.

Rea SL, Walsh JP, Layfield R, Ratajczak T, Xu J. SCGH New insights into the role of sequestosome 1/ p62 mutant proteins in the pathogenesis of Paget’s disease of bone.

Endocr Rev. 2013 Aug;34(4):501-24.

Remnant EJ, Good RT, Schmidt JM, Lumb C, Robin C, Daborn PJ, Batterham P. Uni Melb Gene duplication in the major insecticide target site, Rdl, in Drosophila melanogaster.

Proc Natl Acad Sci USA. 2013 Aug 19.

Trinajstic K, Sanchez S, Dupret V, Tafforeau P, Long J, Young G, Senden T, Boisvert C, Power N, Ahlberg PE. Curtin Uni Fossil musculature of the most primitive jawed vertebrates.

Science. 2013 Jul 12;341(6142):160-4.

Wiederman SD, Shoemaker PA, O’Carroll DC. Univ of Adelaide Correlation between OFF and ON channels underlies dark target selectivity in an insect visual system.

J Neurosci. 2013 Aug 7;33(32):13225-32.

Wong JJ, Ritchie W, Ebner OA, Selbach M, Wong JW, Huang Y, Gao D, Pinello N, Gonzalez M, Baidya K, Thoeng A, Khoo TL, Bailey CG, Holst J, Rasko JE. Centen Inst, USyd Orchestrated intron retention regulates normal granulocyte differentiation.

Cell. 2013 Aug 1;154(3):583-95.

Zanker D, Waithman J, Yewdell JW, Chen W. La Trobe Uni Mixed proteasomes function to increase viral peptide diversity and broaden antiviral CD8+ T cell responses.

J Immunol. 2013 Jul 1;191(1):52-9.

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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.

Annual Bioprocessing Network Conference

October 22-24, Gold Coast The 2103 BioProcessing Network Conference will gather researchers, manufacturers, suppliers and others with an interest in creating an innovative environment for bioprocessing. Applicable to biotherapeutics, biofuels and food processing, the bioprocessing conference promises to be informative and provide networking opportunities across the sector. A keynote presentation will be given by Dr Tony Bradshaw, Director of BioProcessUK, HealthTech and Medicines Knowledge Transfer Network, and other sessions will encompass new research, emerging technologies case studies, and regulatory and commercial considerations in bioprocessing. www.bioprocessingnetwork.com.au/Conferences.html

ComBio2013 September 29-October 3, Perth

5th Asia-Pacific NMR Symposium and 9th Australian & New Zealand Society for Magnetic Resonance October 27-30, Brisbane

www.asbmb.org.au

Australasian College for Infection Prevention and Control Conference September 30-October 2, Gold Coast

www.acipcconference.com.au

2nd Annual NHMRC Research Translation Faculty Symposium - from Bench to Bourke: improving practice, policy and commercialisation October 2-3, Sydney

www.nhmrc.gov.au/media/events/2013/2ndannual-nhmrc-symposium-researchtranslation Australasian Genomic Technologies Association 2013 Conference October 13–16, Gold Coast

http://amataconference.com.au/2013/ Joanna Briggs Institute International Convention - The 2013 campaign for getting evidence into policy October 21-23, Adelaide

http://2013convention.joannabriggs.org/

Annual Bioprocessing Network Conference October 22-24, Gold Coast

www.bioprocessingnetwork.com.au/ Conferences.html

The Australasian Bioenergy and Bioproducts Symposium 2013 October 25, Brisbane

www.tabbs.com.au

http://apnmr2013.org

15th World Conference on Lung Cancer October 27-31, Sydney

www.2013worldlungcancer.org Australia Biotech Invest October 28-29, Melbourne

http://ausbiotechinvest.com/ Association of Biosafety for Australia and New Zealand 3rd Annual Conference October 29-November 1, Auckland, New Zealand

www.absanz.org.au/Conference%202013. html

Australian Society for Medical Research 52nd Annual Scientific Conference November 17-20, Ballarat, Vic

www.asmr-nsc.org.au/

Laboratory Management & Design Conference November 18-20, Brisbane

www.labmanagers.org.au/

HPLC 2013 - 40th International Symposium on High-Performance-Liquid-Phase Separations and Related Techniques November 18-21, Hobart

www.hplc2013-hobart.org

Australian Society for Biophysics Annual Meeting November 24-27, Melbourne

www.biophysics.org.au/Meetings/2013/ index.html

International Symposium on Computational Models for Life Sciences November 27-29, Sydney

http://cmls-conf.org/2013/

Australasian Flow Cytometry Group 36th Annual Meeting November 28-30, Wellington, New Zealand

www.malaghan.org.nz/afcg2013

5th Congress of the International Society for Applied Phycology 2014 June 22-27, 2014, Sydney

www.isap2014.com

2014 International Biophysics Congress August 3-7, 2014, Brisbane

www.iupab2014.org

www.ausbiotech.org

15th International Conference on Systems Biology September 13-19, 2014, Melbourne

2013 Agriculture & Food Biotechnology Symposium November 1, Brisbane

ComBio2014 September 28-October 2, 2014, Canberra

www.ausbiotechnc.org/

www.asbmb.org.au

9th World Sponge Conference November 4-8, Fremantle, Western Australia

AusBiotech 2014 October 28-31, 2014, Gold Coast

www.aims.gov.au/web/sponge/home

www.ausbiotech.org

International Marine Biotechnology Conference November 11-15, Brisbane

Australian Health and Medical Research Congress November 16-19 2014, Melbourne

AusBiotech 2013 October 29-November 1, Brisbane

www.imbc2013australia.com/

www.emblaustralia.org

TBC

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