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The University of Queensland Diamantina Institute “turning scientific discoveries into better treatments”

2011 Annual Report

DIAMANTINA INSTITUTE


Contents 1 Vision Statement 2 2011 Research Highlights 5 Governance and Organisation 6 Chair’s Report 7 Director’s Report 8 2011 Research Impacts 16 16 Engagement 16 16 Fast Facts 17 17 Working with our Clinical Colleagues 20 Commercialisation Update 21 Relocating into the Translational Research Institute (TRI) 22 Researchers Awards 23 Seminars 24 Studying at The UQ Diamantina Institute

24 25 26 28 30 31 32 33 34 35 36 37 38 39

The Pursuit of Excellence Student Awards Student Experiences SPARQ-ed Senior Researchers Dr Antje Blumenthal Professor Matt Brown Dr Marcel Dinger Professor Ian Frazer Associate Professor Brian Gabrielli Professor Tom Gonda Dr Michelle Hill Dr Graham Leggatt Associate Professor Nigel McMillan

40 Dr Ali Naderi 41 Associate Professor Nicholas Saunders 42 Dr Fiona Simpson 43 Dr Raymond Steptoe 44 Dr Gethin Thomas 45 Professor Ranjeny Thomas 46 Professor Peter Visscher 47 Dr James Wells 48 Publications 52 Collaborations 54 Granting Bodies and Donors 55 Grants 60 Financials 61 Occupational Health and Safety


Vision Statement Our vision is to improve human health. Our mission is to translate basic science into better treatments. Since its inception, The University of Queensland Diamantina Institute has supported research of the highest quality with the aim of improving human health. We will build on our key attributes; these are our focus on translational health, our dedication to research excellence, our ability to work in partnership and our integration of clinicians with basic science to drive our mission: turning scientific discoveries into better treatments. In 2012 we move in the Translational Research Institute (TRI) which will bring together over 700 scientists from four partnering institutions (The University of Queensland, Mater Medical Research Institute, Queensland University of Technology and Queensland Health) with strong independent and collaborative research track records in human diseases. We view this as a time of great opportunity and synergy to bring scientific discoveries to human health on a global scale.

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2011 Research Highlights Professor Matt Brown was recognised by

Associate Professor Nick Saunders was awarded a

The University of Queensland as one of its leading researchers based on research performance and was awarded a Senior Principal Research Fellowship from the National Health & Medical Research Council.

Cancer Council Queensland Senior Research Fellowship to continue his research into the early diagnosis and treatment of epithelial cancers.

Professor Ian Frazer was elected a Fellow of the Royal

Research Foundation Excellence award for his research into the cause and cure of brain cancer.

Society of London. The Royal Society, a 350-year old scientific academy, encompasses the most distinguished scientists from across the globe. Current and previous Fellows include Michael Faraday, Stephen Hawking and Isaac Newton.

Dr Ray Steptoe was awarded a prestigious Australian Research Council Future Fellowship that will allow him to continue to work on new therapies for diseases of immune regulation and tolerance.

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Dr Angus Harding was awarded a University of Queensland

As a measure of recognition of innovation and translation,

Professor Ranjeny Thomas was awarded a finalist in the Australian Innovation Challenge for her ground-breaking research that has resulted in the world’s first clinical trial for a vaccine against rheumatoid arthritis.

Dr Peter Darben, The University of Queensland Diamantina Institute’s SPARQ-ed Co-ordinator, was recognised as part of National Science Week by being named as a winner of the 2011 Peter Doherty Awards for Excellence in Science and Science Education.


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Governance and Organisation The University of Queensland Diamantina Institute is governed by an Advisory Board, which provides advice to the Director on the strategic direction of the Institute. The Scientific Advisory Committee assists the Director by providing critical review of the scientific programs of the Institute. Scientific Advisory Committee:

Advisory Board: Professor Deborah Terry (Chair) Professor Max Lu Professor Alan Bernstein OC Professor Nick Fisk Professor Stephen Walker

Professor Peter Gray Dr Greg Bitomsky Mr Malcolm McBratney Dr David Theile Professor Ranjeny Thomas

Professor Alan Bernstein OC (Chair) Professor Peter Donnelly FRS Professor Ashley Dunn

Professor Ian Caterson Professor Jim Watson Professor Melissa Brown

Deputy Vice Chancellor Academic UQDI Scientific Advisory Committee

Institute Director

UQDI Advisory Board

Deputy Director Research

Deputy Director Education

Deputy Director Operations

Research Groups

Postgraduate Student Admin

Research Infrastructure Manager

Administration

Laboratory Services

HR/Finance

IT

Marketing/ Communications

Specialist Facilities

Research Administration Advancement 5


Chair’s Report application of preventative methods and vaccine application against cervical cancer in developing countries. The excellence of UQDI researchers has been further recognised with various awards, prizes and Fellowships. Professor Matt Brown was recognised by The University of Queensland as one of its leading researchers based on research performance and was also awarded a Senior Principal Research Fellowship from the National Health & Medical Research Council. Dr Ray Steptoe was awarded an Australian Research Council Future Fellowship for his work in immunology; Associate Professor Nick Saunders was awarded a Cancer Council Queensland Senior Fellowship for his work in epithelial cancers and Professor Ranjeny Thomas was recognised in the Australian Innovation Awards for her work in vaccine development. A further sign of success and of the high quality of research training provided within the Institute, a number of the Institute’s students were awarded prizes for research excellence in national competitions.

I am delighted, on behalf of The University of Queensland Diamantina Institute’s (UQDI) Advisory Board, to present the Institute’s 2011 Annual Report. The past year has seen some significant changes within the Institute and I congratulate the Institute on continuing to excel in its endeavours to translate biomedical research discoveries to the clinic. I both formally welcome and congratulate Professor Matt Brown on his appointment as Director of the Institute. Professor Brown’s expertise in immunology, genomics and rheumatology have long been of value to the Institute and he is recognised as a world-leader in near-patient translational research in a variety of diseases, but particularly inflammatory arthritis. Professor Brown’s past experiences in leadership positions at The University of Oxford have stood him in good stead in 2011, during a period of transition and opportunity for the Institute. UQDI researchers continue to work closely with clinicians and patients in their key areas of research into autoimmune disease and cancers. They have identified novel diagnostic, therapeutic and preventative discoveries in chronic disease. New diagnostic therapies are being developed to help with the early diagnosis and accurate treatment of acute myeloid leukaemia (AML) and head and neck cancers. Researchers are working with industry to bring to clinical trial the world’s first vaccine against rheumatoid arthritis and other research has discovered potential new therapies for patients suffering type 2 diabetes. UQDI researchers aim to have a global impact in health outcomes and this is evidenced by the continuing

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UQDI continues to expand its collaborative force and high calibre recruitments. In association with the Queensland Brian Institute (QBI), UQDI has further strengthened research ties with China following the opening in Shanghai of a joint laboratory dedicated to exploring how genes influence brain development and function. Professor Peter Visscher has joined the Institute, recruited from the Queensland Institute of Medical Research. A world-leader in quantitative genetics, Professor Peter Visscher strengthens ties across QBI and UQDI, and enforces its reputation as a leader in qualitative and quantitative genomics. The Institute has further recruited emerging research leaders in skin cancer and immune responses to disease. I welcome these recent recruits to the Institute. Looking forward, the UQDI will move into the Translational Research Institute (TRI) in late 2012 and will join a cohort of up to 700 researchers investigating chronic disease and infection. The Institute is undergoing a period of expansion in preparation for the move. It is strengthening its ties with the Princess Alexandra Hospital, non-government agencies and patient advocacy groups to continue to ensure a clinically-relevant research program that maximises upon the opportunities afforded by relocation into the TRI. I look forward to working with Professor Brown during this exciting phase in the Institute’s development.

Professor Deborah Terry Vice-Chancellor, The University of Queensland Chair, The University of Queensland Diamantina Institute Advisory Board


Director’s Report In 2011, The University of Queensland Diamantina Institute (UQDI) started a new era of academic expansion to mature an environment of intellectual innovation and capabilities, supported by leading-edge technologies, with the goal of finding solutions to the prevention, early diagnosis and treatment of chronic disease. As newly appointed Director, it was particularly gratifying to note that UQDI researchers were awarded more than $4.6m in new funding by the National Health and Medical Research Council and the Australian Research Council, achieving grant successes well above the national average. I congratulate Dr Ray Steptoe, who was awarded a prestigious Australian Research Council Future Fellowship; Associate Professor Nick Saunders for the award of a Cancer Council (Queensland) Senior Research Fellowship; and Dr Angus Harding, who was awarded a UQ Foundation Research Excellence Award. This year also saw further development of the UQ Centre for Clinical Genomics (UQCCG), one of the largest genomic centres in the Southern Hemisphere and in Asia. UQCCG, a joint initiative between UQ, UQCCR and UQDI, has resulted in a major research facility for the University, housing world-leading infrastructure in genomics and bioinformatics and supported by specialist staff trained in genomic medicine. It was particularly gratifying to note that UQDI’s international reputation for research excellence in genomic medicine resulted in the recruitment of Professor Peter Visscher, one of the world’s leading authorities in quantitative genomics, whose work concentrates on understanding the influence of genetic changes at a population level, and on development of approaches to predict the risk of developing common diseases using genetic data. Critical to UQDI’s research mission is its dynamic research student body and I am pleased to report that 3 students submitted their theses in 2011 with a total of 10 PhD degrees awarded. A further 6 PhD students and 1 MPhil student are expected to graduate in 2012. The Institute is placing great emphasis on expanding our student population including both Australian and international students, and we hope to more than double our student numbers over the next four years. A particular priority will be the training of new clinician-scientists; a group of researchers who will be critical for translation of basic research findings into clinical applications and practice. In addition to research training, UQDI values its outreach programs, working with the Queensland Government Department of Education and Training (DET) to coordinate the SPARQ-ed program. SPARQ-ed brings high school students and their teachers into the laboratory to conduct experiments themselves and to expose them to the lives and experiences of scientists at all different stages of their careers, helping stimulate their imaginations and understandings of the frontiers of science. Since 2009, more than 2,000 students and 200 teachers have participated in programs coordinated by SPARQ-ed. Granted credit for UQ entry under the Assessable Module Bonus

Rank Scheme, this course also provides educational advantage to participating students. I was particularly proud to see Dr Peter Darben, who runs our SPARQ-ed program, awarded the 2011 Peter Doherty Award for Excellence in Science Education, a prestigious award recognising the outstanding effort he makes in promoting science to high school students. We look forward to working with DET and philanthropic organisations to continue SPARQ-ed into the future. I am also looking forward to the relocation of UQDI into the Translational Research Facility (TRI) in late 2012. As the building continues to take shape and form, it is inspiring to imagine the enormous synergies that will be actualised through the collocation of 700 researchers engaged in biomedical translational research. The additional space afforded to UQDI will enable us to more than double the Institute’s research staff over the next four years, greatly expanding our research capacity. The Biopharmaceuticals Australia manufacturing facility for biotherapeutics products, housed adjacent to TRI, will greatly improve our capacity to translate research discoveries to the clinic; our scientific goal. It is appropriate to acknowledge the support granted to UQDI. In amongst the funding provided by the Australian and National Health and Medical Research Councils, UQDI receives support from a wide number of non-government organisations that are focused on finding solutions to cancers, autoimmune diseases and infection. Private benefactors have also been extremely generous in their support and I sincerely thank our Research Partners for joining us in our mission of preventing, diagnosing and treating chronic disease.

Professor Matthew Brown Director, The University of Queensland Diamantina Institute

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2011 Research Impacts

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Genetic interactions in spinal arthritis and psoriasis shed light on disease susceptibility Patients suffering from a painful form of arthritis which fuses bones in the spine and pelvis may have hope for the future development of new treatments. Researchers at The University of Queensland Diamantina Institute (UQDI) have made a major breakthrough in the understanding of the molecular mechanisms underlying the disease, ankylosing spondylitis (AS).

Canada to embark upon the largest study in history into the genetic causes of AS. Their research has identified eight new genes that help clarify previously unexplained aspects of AS. In particular, these genes help explain why bone formation occurs and why some AS patients also develop the conditions Inflammatory Bowel Disease and/or psoriasis.

AS causes the immune system to attack the spinal and pelvic joints, leading to chronic inflammation. Unlike other forms of arthritis where inflammation leads to bone loss, AS results in bone growth and/or can consequently cause the spine and or pelvis to become fused into a fixed position. AS affects up to 80,000 Australians and currently there is no treatment available that causes disease remission. However, a new discovery by researchers at UQDI could help pave the way for the development of new treatments.

Professor Matt Brown commented that the findings shed light on a 40 year old genetic mystery. In the 1970s, it was discovered that nearly all AS patients carried a particular gene called HLA-B27. According to Professor Brown, “The link between AS and HLA-B27 is one of the strongest known genetic associations of any common disease. However, the precise role this gene plays in AS has never been clear until now.�

Headed by Professor Matt Brown, UQDI scientists formed an international consortium with research groups in the UK, USA and

He and his colleagues have discovered that a mutation in a second gene, ERAP1, only appears in HLA-B27 positive AS patients. The finding suggests these two genes work together in AS to disrupt the way the cells in the spinal and pelvic joints interact with

the immune system. This, in turn, may help explain the strong immune reaction seen in AS, and is expected to open up new avenues in the search for new drug treatments. Interestingly, Professor Brown and his colleagues also found a similar genetic connection in psoriasis. Mutations in ERAP1 only changed the susceptibility to the disease in patients with the high risk variant of HLA-C, a gene closely related to HLA-B27 identified in AS. Both studies, published in the prestigious journal Nature Genetics (November 2010 and August 2011 issues, respectively), also have far reaching implications beyond psoriasis and AS. The identification of interactions between these particular sets of genes is the first solid evidence of two genes working in concert to determine susceptibility in any human disease. The Australo-Anglo-American Spondyloarthritis Consortium (TASC) & the Wellcome Trust Case Control Consortium 2 (WTCCC2); Nature Genetics (2011) 43: 761-767.

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A novel class of inhibitors specifically affects cancer cells, but leaves normal cells unharmed Melanoma, a particularly aggressive form of skin cancer, is the fourth most common cancer in Australia, and survival rates are low once the disease has spread (metastasised) to other organs. Researchers at The University of Queensland Diamantina Institute (UQDI) have demonstrated that a novel class of inhibitors which target a known Achilles heel of cancer cells could provide a new treatment approach for metastatic melanoma. Our bodies are constantly producing new cells through a process called cell division, in which a parent cell divides into two identical daughter cells. This process takes place several trillion times in a human’s life, ensuring growth in our early years, and the replacement of dying cells once we are adults. Before cell division can occur, cells must accurately copy their genetic material. Mistakes in gene duplication are a major factor in birth defects and the development of diseases, most notably cancer.

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The cell cycle, i.e. the progressive series of steps that leads from a single cell to two identical daughter cells, incorporates a number of so-called checkpoints, where duplication mistakes are detected and the cell cycle is halted until the damage is repaired, or cell death is promoted when the damage cannot be repaired. In certain cancer cells, including melanomas, one or several of these checkpoints are disabled, making the cells dependant on the remaining checkpoint(s) to avoid cell death. Associate Professor Brian Gabrielli and his colleagues at UQDI, in association with their industry partner, have shown that low concentrations of certain inhibitors of checkpoint kinase 1 (Chk1), a particular checkpoint protein, has deadly effects on certain melanoma cells, but leaves normal cells unharmed. Current treatment options for metastatic melanoma are limited, and the five year survival rate for patients is 2-3%, highlighting a desperate need for improved therapies.

In a bid to enhance patient outcomes, Associate Professor Gabrielli has joined forces with Professor Grant McArthur and Dr Petranel Ferrao at the Peter MacCallum Cancer Centre in Victoria. The team has been awarded a Cancer Australia grant to identify markers that indicate susceptibility of different cancer types to Chk1 inhibitors. Once suitable markers have been found, it will be possible to predict whether a cancer patient will respond to treatment with these inhibitors. Although a routine clinical use of Chk1 inhibitors is still in the future, the work of Associate Professor Gabrielli and his collaborators will form the basis of better treatment options for metastatic melanoma patients. Brooks K, Oakes V, Edwards B, Ranall M, Leo P, Pavey S, Pinder A, Beamish H, Mukhopadhyay P, Lambie D, Gabrielli B; Oncogene (2012) advance online publication, doi: 10.1038/onc.2012.72


A major player in the development of skin cancer identified Squamous cell carcinoma (SCC) is a skin cancer arising from the outer layers of the skin. Although not as widespread as other forms of skin cancer, SCC is particularly dangerous since it often spreads (metastises) to other parts of the body. SCCs that have spread are potentially life threatening and are associated with high mortality rates. Associate Professor Nick Saunders and his colleagues at The University of Queensland Diamantina Institute (UQDI) and The UQ School of Biomedical Sciences are investigating a family of proteins that could hold the key to transforming SCC cells back into normal cells. SCC of the skin mainly affects skin areas exposed to direct sunlight, such as the face, neck, forearms and lower legs. When skin cells are exposed to excessive

sunlight, their DNA becomes damaged, which affects many of the normal functions of the skin. On a cellular level, the most striking characteristic of both sun damaged skin cells and skin cancer cells is their inability to mature. Associate Professor Nick Saunders and his collaborators at UQDI have investigated a family of proteins called E2Fs that act as switches that decide whether genes are turned “on” or “off”. Significantly, members of the E2F family appear to be important regulators of skin cell maturation, with one E2F protein, E2F7, acting as a brake on maturation. Associate Professor Saunders and his team have found that the levels of E2F7 are 200-fold higher in SCC than in normal squamous cells. They proposed that these high levels of E2F7 prevent normal maturation of skin cells and are one of the reasons skin

cancers form. Associate Professor Saunders and colleagues showed that inhibition of E2F7 can cause cells that were previously stuck in duplication mode (as happens in cancers) to mature. This suggests that blocking E2F7 in skin cancer cells would allow them to mature, and would stop the growth of the cancer. Associate Professor Saunders and his team are investigating whether E2F7 could be a promising target for a future SCC therapy. Hazar-Rethinam M, Cameron SR, Dahler AL, Endo-Munoz LB, Smith L, Rickwood D, Saunders N; Journal of Investigative Dermatology (2011) 131: 1077-1084.

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Insights into the regulatory mechanisms of our immune system have implications for autoimmune diseases Researchers at The University of Queensland Diamantina Institute (UQDI) and their collaborators have shed light on the decade old question of how specialised immune cells regulate our immune response. Their findings, published in the May 2011 issue of Proceedings of the National Academy of Sciences USA, help our understanding of tumour and viral immunity as well as autoimmune diseases. Our immune system is a complex network of organs, cells and molecules protecting us against invading pathogens such as bacteria and viruses, but also against abnormal cells such as tumour cells. One of the challenges for the immune system is to recognise ‘self’ and ‘non-self’, i.e. differentiate between the body’s own healthy cells and invaders or tumour cells. Specialised cells called T-cells regulate other immune cells to ignore the former, but destroy the latter.

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However, this regulation sometimes fails, resulting in autoimmune disorders (such as rheumatoid arthritis or type 1 diabetes), in which the immune system attacks normal body cells, or immune deficiencies, so that invading bacteria and viruses are no longer recognised and destroyed. Particular T-cells, called regulatory T-cells or Treg, have been known for decades to be directly involved in controlling autoimmunity. How exactly they accomplish this task in the body, however, has remained unclear. UQDI’s Dr Raymond Steptoe and his colleagues have brought us a step closer to understanding the molecular mechanisms of T-cell regulation. They showed that Treg cells mop up the signalling molecule IL-2 that normally triggers another type of T-cell to multiply and mature into fully functional killer cells. In addition, they have identified a feedback mechanism, in which IL-2

released by these maturing T-cells, activates Treg cells. As a result, disturbances in the number or function of Treg cells (and the resulting high IL-2 levels) can have far reaching effects on both immune response and autoimmune disease. In Australia, approximately 1 in 20 people, or more than 1.1 million Australians, are affected by autoimmune diseases. There are currently more than 80 known autoimmune diseases, and while a wide range of treatment options are available, there are no cures for these diseases. Dr Steptoe is investigating how manipulating the balance between IL-2 and Treg could be utilised to develop therapies for the prevention and cure of autoimmune disease. McNally A, Hill GR, Sparwasser T, Thomas R, Steptoe RJ; PNAS (2011) 108(18): 7529-7534.


A new marker for type 1 diabetes could provide early diagnosis and better therapy Type 1 diabetes (T1D) is an autoimmune disease that affects over 120,000 Australians, with most sufferers diagnosed during childhood. New therapeutic approaches have shown promising results, but timing of these therapies was found to be crucial for success. Researchers at The University of Queensland Diamantina Institute (UQDI) have established that monitoring the increased production of interleukin 1b (IL-1b; a protein that stimulates inflammation) could be used as treatment and for the early diagnosis of pre-diabetic states. In T1D, misguided immune cells attack and ultimately destroy the insulin producing b-cells of the pancreas. Without insulin, glucose concentrations in the blood and urine of T1D patients rise to dangerous levels, and T1D is eventually fatal if not treated with insulin. In recent years, new forms of therapy aimed at preventing the destruction of b-cells have been trialled with varying success. In one of these approaches, called tolerising immunotherapy, the immune system is trained not to attack the b-cells, while in

the other, called cytokine blockade, messenger molecules (cytokines) are prevented from initiating an inflammatory response that can lead to destructive tissue damage. However, since T1D is a progressive disease, each of these approaches only works at certain stages, and determining the right point in time to use one or the other is still a diagnostic challenge. Professor Ranjeny Thomas and her collaborators at UQDI, the St. Vincent’s Institute and the Walter and Eliza Hall Institute have shown that in the early stages of T1D, high levels of IL-1b are central in directing the autoimmune response by inducing certain regulatory cells of the immune system to transform into so called T-helper 17 cells, which are known to play a role in autoimmune disease, inflammation and tissue damage. Chronic inflammation even before disease onset has been documented in children at high risk of developing T1D. The results presented by Professor Thomas and her colleagues demonstrate that this inflammation

is most likely linked to increased quantities of IL-1bβbeing produced. Blood levels of IL-1bβcould serve as an early prognostic marker in high risk children, providing an opportunity to start tolerising immunotherapy early in the disease progression. This would greatly increase the likelihood of success, i.e. delaying or even preventing the destruction of b-cells. In addition, at a certain stage of the diseas, IL-1b levels are predicted to drop, signalling a necessary switch in therapy strategy from tolerising immunotherapy to cytokine blockade. Professor Thomas and her colleagues are now investigating the presence of a genetic signature for T1D in children that have recently been diagnosed, as well as children at high risk of developing diabetes (i.e. first degree relatives of T1D patients) to further improve the potential for early diagnosis and better timing of immunotherapy. Bertin-Maghit S, Pang DM, O’Sullivan B, Best S, Duggan E, Paul S, Thomas H, Kay TWH, Harrison LC, Steptoe R, Thomas R; Diabetes (2011) 60(1): 248-257.

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A novel diagnostic method for amyloidosis can assist clinicians in choosing the right therapy The term “amyloidosis� covers a diverse group of diseases resulting from abnormal depositions of misfolded, insoluble proteins that can alter or impede crucial body functions. Since treatment options need to be tailored to each type of amyloidosis, accurate identification of the type of deposited protein is crucial. Researchers at The University of Queensland Diamantina Institute (UQDI) have introduced a novel diagnostic method for amyloidosis which has already benefited patients at the Princess Alexandra Hospital (PAH). Proteins fold into very specific shapes to accomplish their tasks in the body. In amyloidosis, this specificity is lost and misfolded proteins aggregate and form insoluble deposits either systemically (i.e. all over the body) or localised to one organ. The symptoms of amyloidosis can be diverse, depending on the location of these amyloid deposits. The condition can go undetected or be life threatening, for example, when the deposits form in the heart. About half of all amyloidosis patients

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also suffer from kidney damage that can progress to kidney failure and most of them show protein in their urine (proteinuria). The gold standard of amyloid detection, the staining of tissue samples with a special dye called Congo Red, clearly identifies damaging amyloid protein deposits in tissues. However, this technique cannot be used to determine which protein is the culprit – an essential pre-requisite for choosing the correct therapy approach. For example, AL amyloidosis, the most common form of amyloidosis, is routinely treated with chemotherapy or stem cell transplantation. This form of therapy would be ineffective and dangerous for other forms of amyloidosis. Working with Drs Peter Mollee and Patricia Renaut at Pathology Queensland, Dr Michelle Hill and her team at UQDI have been working on a method to directly identify the culprit protein from tissue samples used for Congo Red staining. The protein deposits are precisely cut out of the sample using a narrowly focused

laser beam in a process called laser microdissection. The proteins are then dissolved, analysed and identified through comparison of the data with a vast protein database. With this information, the clinician can tailor a treatment program for each patient, potentially improving the success rates and limiting side effects. Dr Hill and her colleagues are working on further streamlining their technique by limiting the amount of sample handling and time necessary for analysis, as well as establishing a computer based method for protein identification. Drs Hill, Mollee and Renaut plan to take their procedure from an experimental method to a validated test in 2012. Through this work, the Amyloidosis Diagnosis and Treatment Centre at PAH has the potential to become a reference diagnosis facility for amyloidosis in Australasia. Loo D, Mollee PN, Renaut P, Hill MM; Journal of Biomedicine and Biotechnology (2011): 754109.


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Engagement

Fast Facts > 18 research leaders > 225 research and support staff > 48 enrolled research higher degree students > 130 collaborations > Two spin off companies: Dendright and Coridon > 90 million doses of the cervical cancer vaccine administered in 124 countries

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Dr Michelle Hill

Dr Fiona Simpson Dr Marcel Dinger

Working with our Clinical Colleagues Dr Michelle Hill Dr Michelle Hill joined The University of Queensland Diamantina Institute in 2009 with a NHMRC Career Development Award. Her background is in cell signalling and membrane microdomain research, with technical expertise in proteomics. She has extensive international post-doctoral experience in Switzerland and Ireland. Since returning to Australia, her work with Professors Rob Parton and John Hancock (UQ) led to seminal discoveries in caveolae biology. Dr Hill established the Cancer Proteomics Group at UQDI with the twin aims of developing new non-invasive tests to diagnose cancers, and to understand how caveolae membrane microdomains contribute to cancer development and progression. She has established a high throughput proteomics and mass spectrometry facility at the Institute. Using the cutting edge instrumentation, her group has developed novel workflows for biomarker identification and are currently applying these to several cancers, including prostate cancer, oesophageal adenocarcinoma and canine haemangiosarcoma. Dr Hill believes in an interdisciplinary approach in translational research and collaborates with a broad spectrum of researchers from clinical, biomedical to computational biologists. Her work has already resulted in improved diagnosis techniques for amyloidosis at Queensland Pathology.

Dr Fiona Simpson Dr Fiona Simpson started her research group at The University of Queensland Diamantina Institute in 2010 with an NHMRC Career Development Award. Her background is in cell trafficking and signalling research, with expertise in biochemistry and cell biology. After completing a PhD at Cambridge (UK) and postdoctoral studies as a Wellcome Trust Fellow at the Scripps Research Institute, La Jolla in the USA, Simpson came to Australia as a Juvenile Diabetes International Research Fund Research Fellow to work with Professor David James (UQ). On establishing her independent research group at The University of Queensland Diamantina

Institute, Dr Simpson has used her cell biological and trafficking expertise to address human epithelial cancer research. Working with PAH clinicians, the Simpson laboratory has developed a technique to observe the movement of tumour cell receptors in response to activation in live human tumour tissue. This technique is being used to look at how the receptors behave in the tumour environment and how this affects patient responses to modern targeted therapies. The results of this work have now led the group to test a family of small molecules which may improve patient responses to these therapies. The Simpson group also work on characterising the function of a family of proteins involved in cellular trafficking which have been implicated in cancer metastasis, in order to find diagnostic markers for cancer diagnosis and possible new therapeutics. The laboratory believes strongly in using the solid base of basic research advances discovered by the cell trafficking and signalling fields, in translational research to benefit cancer patients.

Dr Marcel Dinger Dr Marcel Dinger has been an NHMRC Senior Research Fellow at The University of Queensland Diamantina Institute since 2011. In 2003, Dr Dinger received his PhD From The University of Waikato. In 2009, he was awarded a Smart Futures Fellowship from the Queensland State Government and in 2012, received an NHMRC Career Development Award. Although the sequence of the first complete human genome was determined more than a decade ago, Dr Dinger says we only understand the functions of a tiny fraction of it. However, with the dramatic reduction in the cost of DNA sequencing, it has become possible to find answers to questions that we did not even know to ask 20 years ago. Dr Dinger is using DNA sequencing to track the genetic changes that occur in the early stages of melanoma. In order, he hopes to identify new molecular markers to identify the disease when it can still be easily controlled and find new targets for drugs to treat malignant melanoma.

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Collaboration advances early diagnosis of skin cancer The intensive collaboration between members of my mostly clinically-focused dermatology research group and the translational scientists from UQDI has fundamentally changed my perception of clinical research. I believe that the daily and constant interaction between academic clinicians and scientists regarding their mutual research projects is the vital ingredient for successful translational research. Based on my experience on this interaction, I am enthusiastic about the research future in skin cancer on the Princess Alexandra Hospital campus.

Our recent research is driven by the hypothesis that the dermoscopically observed morphological features of benign naevi and primary melanomas can be used as a clinical tool for rapid and accurate assessment of molecular changes that predict a high risk of neoplastic transformation to melanoma. Further, we are convinced that linking genetic analysis of individual dermoscopic features of naevi with support vector machine assisted image analysis will provide a new dimension for objective diagnosis and prognosis of naevi and melanoma. Our clinical naevus/melanoma research benefits immensely from the collaboration with Associate Professor Brian Gabrielli and Dr Marcel Dinger from The University of Queensland Diamantina Institute, and Dr Duncan Lambie from the Princess Alexandra Hospital Pathology Department. This collaboration allows us to characterise excised naevi and early melanomas with our refined feature list (histopathology, immunohistochemistry, transcriptomic and genotypic analysis) and independently subject these lesions to an artificial intelligence algorithm, which has been recently developed by Stephen Gilmore from The University of Queensland Dermatology Research Centre.

Professor Peter Soyer MD FACD Director of Dermatology, Princess Alexandra Hospital, Dermatology Research Centre, The University of Queensland School of Medicine Affiliate Researcher The University of Queensland Diamantina Institute The total number of naevi (birthmarks) is an important risk factor for melanoma, with 42% of people with high mole counts, going on to develop melanoma. Thus, naevi represent a unique opportunity to observe premalignant lesions that are likely to be significant for transformation to primary melanoma especially in high risk patients. The practical question of how to utilise this opportunity in an efficient and effective manner has been addressed using the imaging technique of dermoscopy, a clinical research field in which I have been working for more than 20 years (Soyer HP et al. Lancet. 1987 Oct 3:803).

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A second exciting research project in collaboration with Professor Ian Frazer (TRI/UQDI) and Professor Matt Brown (UQDI) focuses on sequencing the transcriptoma of actinic keratosis to determine whether papillomavirus and/or polyomavirus are present in these most common keratinocyte cancer precursors. With Tarl Prow from our group, we are developing a microbiopsy device which will allow us tissue sampling for molecular analysis without scarring or the need for local anaesthesia in the future. We have just recently submitted an NHMRC project grant titled “Developing an improved dermoscopic method for identifying molecular changes in naevi driving early stage melanoma” by Soyer (UQ DRC), Gabrielli (UQDI), Gilmore (UQ DRC), Lambie (PAH Pathology) and Dinger (UQDI). Additionally, the virus hunt project in actinic keratosis (the most relevant squamous cell carcinoma precursor in man) held in collaboration with Professor Ian Frazer (TRI/UQDI) and Professor Matt Brown (UQDI) has been granted funding from the PA Research Foundation and is well underway. In Germany, we have a saying “Gut Ding braucht Weile” (good things take a while) and in this spirit I am convinced that the collaboration between my newly established research centre (established in 2007) and UQDI will flourish in the future.


Improving bone health By understanding the genes affecting growth and development of bone, we will be able to explore new therapeutic pathways to improve bone health for the community, of particular relevance to Australia with its rapidly ageing population. The collaboration between The University of Queensland Centre for Cancer Research at The Royal Brisbane Hospital campus, and The University of Queensland Diamantina Institute researchers will help advance our ability to improve patient outcomes.

Osteoporosis is the commonest metabolic bone disease worldwide, and affects 60% of Australian women, and 30% of Australian men aged 60 years or over. In contrast, skeletal dysplasias are relatively rare bone disorders, but have very serious consequences for affected individuals, often having a major effect upon both quality of life and mortality. There are nearly 400 different recognised skeletal dysplasias, but the underlying genetic cause is only known for about half of these. Working with UQDI’s bone research group led by Professor Matt Brown, our work in osteoporosis aims to discover the genes that influence how our bone strength develops and is maintained in the general population. Our work in skeletal dysplasias aims to discover the genes causing these severe diseases, not only for the sake of the affected individuals but also because these genes shed light upon normal bone growth and development, of relevance for understanding the bone health for everyone in the population. a) We have published a prominent genome-wide association study, identifying the important genes determining bone mass in individuals with either very high or very low bone mineral density, and then demonstrated that these genes are relevant to bone strength in the normal population. Building on this work, we were awarded a grant from the NHMRC to look at the rare variants that drive these observed associations. b) We have published two proof-of-concept papers using next-generation sequencing, a cutting edge genetic technology, to identify the genes causing two separate skeletal dysplasias. In particular, not only did we demonstrate the causative gene, we showed this approach would work both when looking at a small family unit and also when investigating a disease affecting unrelated individuals in the community.

Associate Professor Emma Duncan MBBS MRCP FRACP PhD LMusA Senior Staff Specialist in Endocrinology, Royal Brisbane and Women’s Hospital Affiliate Researcher The University of Queensland Diamantina Institute

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Commercialisation Report by Lisa Bidwell, Commercialisation Manager

The University of Queensland Diamantina Institute (UQDI) has a strong focus on translational research, with the aim of converting basic science into better treatments for patients. As such, commercialisation of our research is well aligned with the Institute’s goals, and the Institute has a long history of working with industry and commercial partners to achieve these goals. Partnerships with Industry The Institute values collaboration with industry and the benefits this can bring, including the development of key research collaborations, the transfer of knowledge, as well as the additional research income that this generates for the Institute. Our research collaboration with CSL in the early 1990s which sought to develop a HPV vaccine, continues to bring benefits to UQDI. The product of that early collaboration, Gardasil, is now sold by Merck in 124 countries around the world, generating royalties for the Institute as well as international recognition for the work of its inventors, Professor Ian Frazer and the late Dr Jian Zhou. In 2011, the vaccine was released in the key market of Japan. In addition, The Centers for Disease Control and Prevention’s immunisation committee in the USA recommended, for the first time, routine use in boys to prevent HPV-related cancers. During 2011, the Institute continued to support our other collaborative and industry partners by performing contract research and supporting the commercialisation of those technologies originating from UQDI. Intellectual property protection The University of Queensland Diamantina Institute’s patent portfolio remains strong and diverse with applications covering a broad range of diagnostic and therapeutic applications in cancer and immunology. A number of provisional and PCT patent applications were filed in 2011 and the outlook for 2012 is promising, with a number of new potentially patentable technologies on the horizon.

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Start-up companies Two start-up companies have been formed, based on technologies developed at UQDI, and 2011 has been a productive year for both of these. Dendright Pty Ltd was founded in 2004 to commercialise a novel immunotherapy for rheumatoid arthritis developed in Professor Ranjeny Thomas’ laboratory. The company has previously been supported by grants from the Queensland Government’s Innovation Start-Up Scheme and the Australian Government’s Biotechnology Innovation Fund. In 2011, Dendright was awarded a seed grant from Janssen-Cilag Pty Ltd in Australia, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, to fund preclinical development of the technology for rheumatoid arthritis. This represents an important collaboration for Dendright and will greatly assist in the future development of the technology. To date, the company has not received external investment, and remains wholly owned by UniQuest, The University of Queensland’s main commercialisation company. Coridon Pty Ltd was founded in 2000, based on work by Professor Ian Frazer’s group, to develop prophylactic and/or therapeutic polynucleotide vaccines for infectious diseases and cancers using its unique optimisation technology. In 2011, Coridon reported positive results indicating its prototype vaccine was 100% effective at protecting animals against HSV-2 infection. On the basis of this, the company secured additional funding from its major investor, Allied Healthcare group, to advance preclinical development of the technology. Education The Institute aims to raise awareness of commercial considerations amongst its researchers through internal seminars and by supporting our postgraduate students to attend commercialisation workshops. It is compulsory for UQDI PhD students to attend the two-day Commercialisation Workshop sponsored by UniQuest, to provide them with early awareness of the significance of commercialisation.


Relocating into the Translational Research Institute (TRI) The University of Queensland Diamantina Institute (UQDI) is one of four research institutions that will move in 2012 into the Translational Research Institute (TRI) building, currently under construction on the Princess Alexandra Hospital campus. 2011 has been a year of intense planning towards this move for UQDI, the Mater Medical Research Institute, Queensland University of Technology’s Institute for Health and Biomedical Innovation, and the Princess Alexandra Hospital’s Centres for Health Research. TRI is purpose-designed to provide a world-class research environment, and state-of-the-art core infrastructure for biomedical translational research, for 700 clinicians and research scientists. The clinical care facilities across the Princess Alexandra and South Brisbane Hospital campuses have recently formed an academic health centre, Diamantina Health Partners, within which TRI will provide much of the research infrastructure.

TRI will provide not only laboratories but also clinical research facilities, which will be located at the new Royal Children’s Hospital and within Princess Alexandra Hospital. Further, the TRI laboratory building will be adjacent to the Biopharmaceuticals Australia building, where DSM biologics will produce clinical grade biopharmaceuticals for clinical trial in Australia and elsewhere. Bringing together four research institutions in the TRI building, with easy access to clinical research facilities and to manufacture of clinical grade research materials, synergise research collaborations and attract further world-leading clinicians and researchers to the campus, speeding up the translation of research on disease into new clinical treatments. We look forward to the opening of the facility in late 2012. Professor Ian Frazer Chief Executive Officer and Research Director Translational Research Institute Dr Kate Johnston Chief Operations Officer Translational Research Institute

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Researcher Awards Linda Bradbury

Tony Kenna

> Best Free Paper by a Rheumatology Healthcare Professional, Australian Rheumatology Association Annual Scientific Meeting

> > >

Matt Brown > NHMRC Senior Principal Research Fellow, NHMRC, 2011-2016 > Q-Index award 2011 (UQ) - in the Top 25 of researchers from The University of Queensland > Honorary Professorship, Second Military Medical University, Shanghai, China > UQDI Paper of the Year

Sandra Pavey > 2011 UQ Postdoctoral Fellowship for Women

Nicholas Saunders > Cancer Council Queensland Senior Research Fellowship

Graeme Clark

Ray Steptoe

> UQDI Jian Zhou travel award

> Australian Research Council Future Fellowship > Runner-up, UQDI Publication of the Year

Emma Duncan > UQDI Best Paper of the Year Award, Runner-Up

Ian Frazer > Fellowship of The Royal Society of London (UK)

Kerry Inder > Young Investigator Award, the Australasian Proteomics Society Conference

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Arthritis Australia Herald Fellowship Princess Alexandra Hospital Young Investigator of the Year Award Australian Rheumatology Association Annual Scientific Meeting 2011 Best Free Paper

Ranjeny Thomas > Finalist, Health section of the Australian Innovation Challenge

Jian Yang > Runner Up, ASMR Queensland Health and Medical Research Awards 2012 (Post-doctoral Researcher)


Seminars for 2011 Professor Warren Alexander

Professor Jenny Gamble

Walter and Eliza Hall Institute of Medical Research

Centenary Institute

Dr Antje Blumenthal

The University of Queensland Diamantina Institute

The University of Queensland Diamantina Institute

Professor Matt Brown The University of Queensland Diamantina Institute

Professor Jonathon Cebon Ludwig Cancer Institute

Professor Georgia Chenevix-Trench Queensland Institute of Medical Research

Associate Professor Barbara Coulson University of Melbourne

Professor Roger Daly Garvan Institute

Dr Ross Dickins Walter and Eliza Hall Institute of Medical Research

Associate Professor Emma Duncan Royal Brisbane and Women’s Hospital

Dr Maree Faux Ludwig Institute

Professor Tom Gonda Professor Phillip Hansbro University of Newcastle

Dr Angus Harding The University of Queensland Diamantina Institute

Professor Bill Heath University of Melbourne

Professor Geoff Hill Queensland Institute of Medical Research

Dr Michelle Hill The University of Queensland Diamantina Institute

Professor David James Garvan Institute

Associate Professor Kiarash Khosrotehrani The University of Queensland Centre for Clinical Research

Dr Matti Lehtinen University of Tampere, Finland

Dr Paul Leo

Associate Professor Nigel McMillan The University of Queensland Diamantina Institute

Dr Ali Naderi The University of Queensland Diamantina Institute

Dr Jamie Nourse Queensland Institute of Medical Research

Associate Professor Nicholas Saunders The University of Queensland Diamantina Institute

Dr Mark Shackelton Peter MacCallum Cancer Centre

Dr Fiona Simpson The University of Queensland Diamantina Institute

Professor Mark Smyth Peter MacCallum Cancer Centre

Dr Ray Steptoe The University of Queensland Diamantina Institute

Dr Catherine Suter Victor Chang Cardiac Research Institute

Dr Gethin Thomas

The University of Queensland Diamantina Institute

The University of Queensland Diamantina Institute

Institute of Molecular Bioscience, The University of Queensland

Professor Charles Mackay

Dr James Wells

Associate Professor Brian Gabrielli

Associate Professor John Maraidason

The University of Queensland Diamantina Institute

Ludwig Institute

Dr Mathias Francois

Monash University

Dr Sally Martin

The University of Queensland Diamantina Institute

Associate Professor John Whitehead Mater Medical Research Institute

The University of Queensland

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Studying at The UQ Diamantina Institute The Pursuit of Excellence The University of Queensland Diamantina Institute (UQDI) seeks to attract the most promising students and clinicians by providing world-class research training opportunities. As a student of the UQDI, you are given the chance to undertake research in an environment dedicated to the pursuit of excellence, where researchers are given the freedom and support to challenge the frontiers of biomedical and translational science. You will be encouraged to develop your research skills, to develop research acumen and you will become an active and employable member of your community - from communication to commercialisation. UQDI students join a stimulating interdisciplinary team of researchers that includes molecular bioinformaticians, immunologists, geneticists, clinicians and biostatisticians. There are currently approximately 50 PhD, Masters and BSc Honours students studying at UQDI and in 2011 the Institute had 10 PhDs and 8 Honours students graduate. Each student is supported by at least two supervisors and a thesis committee to aid in critical assessment of, and smooth progression through, the research project. Further support is provided by the Deputy Director (Education) who oversees all students,

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and a Postgraduate Administration Officer who helps administer procedures. To further expand the breadth of the research experience, students also participate in the UQDI Professional Development Series which incorporates workshops in bioinformatics, ethics, business, grant writing, scientific writing, presentations, dealing with the press, the philosophy of science, and other key areas. The aim of this series is to widen the skills base of our students and to equip them for the diverse career options that are open to high-calibre research higher degree graduates. This series is organised by our in-house Science Writer, who also provides one-on-one support to assist in honing the writing and presentation skills of our student body. UQDI provides travel awards of up to $10,000 to enable students to visit other laboratories and to attend conferences to acquire new skills, establish collaborations and meet future employers. Our past students have gone on to research positions at the premier institutes worldwide including Cambridge, Oxford, Harvard, Johns Hopkins, the MD Anderson Cancer Centre and many other leading universities in Europe and the USA.


Student Awards Helen Benham

Deepak Mittal

> New Investigator Award at the Australian Rheumatology Association Annual Scientific Meeting

> Cancer Council Queensland Travel Award

Kelly Brooks > UQDI Jian Zhou Pre-doctoral Travel Award > UQ Graduate School International Travel Award > Women in Technology PhD Career Start Award > Princess Alexandra Hospital Young Investigator of the Year Award > Runner Up, Student Orals, ASMR Postgraduate Student Conference Award

Jana McCaskill > GSK/AusBiotech Student Excellent Award > Australian Society of Microbiology (ASM) Student Oral Award at the National Australian Virology Society Conference > Finalist in the Women in Technology PhD Career Start Award > Infection and Immunity - Nature Immunology first place poster prize

Dimeng Pang

Miranda Coleman

> Travel Bursary at the Australasian Society for Immunology International Conference

> > > >

Diwakar Ram Pattabiraman

Jomar eBioscience Poster Prize at the Australasian Society for Immunology Annual Meeting FOCIS Travel Award JDRF Travel Award UQDI Travel Award

April Choi > 3 Minute Thesis - Science Faculty Final Runner-Up > 3 Minute Thesis - School of Veterinary Science Winner > Agilent Student Research Award for Lorne Proteomics Conference

IIaria Croci > UQDI Travel Award

> > > > >

Cancer Council Scholarship Leukaemia Foundation Scholarship UQDI Jian Zhou Pre-doctoral Award Graduate School International Travel Award ASMR Postgraduate Runner-Up Award

Felicity Rose > Oxygen Club of California Young Investigator Award at the International Conference on Mechanisms of Action of Nutraceuticals (ICMANS)

Mamdouh Sedhom

Christina Gosmann

> Best Poster at the Australian Society for Immunology International Conference

> Jomar eBioscience Poster Prize at ASI Conference > UQDI Travel Award

Richa Singhania > UQDI Travel Award

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Student Experiences PhD Student Jana McCaskill, UQDI Graduand In the past year I have been fortunate to present my work internally, locally and at national conferences. One of the most memorable experiences from 2011 was winning a trip to the AusBiotech conference in Adelaide which provided exposure to the commercial side of science. These opportunities have provided me with essential presentation and networking skills that I hope to extend by attending an international conference next year. After completing my undergraduate and honours degrees at The University of Queensland, I started thinking about undertaking a PhD. I realised that I loved being in a lab, designing experiments and being part of the scientific community. I chose The University of Queensland Diamantina Institute (UQDI) for my PhD due to the cutting-edge nature of my project, the exceptional facilities offered by the Institute, and the quality supervisors and scientists with whom I now interact and learn from every day. I am now at the end of my second year of my PhD and my project involves using gene-silencing technologies to suppress respiratory viral infections. Our group has taken a bi-functional approach by boosting the efficiency of this gene silencing through recruitment of the immune system to fight infection. This is an innovative method for treating viral infections, by combining novel therapeutic agents with our natural immune defence against viruses. Currently, I’m visiting the CSIRO Australian Animal Health laboratory (AAHL) in Geelong, Victoria. AAHL is quite unique as it combines traditional PC2 facilities ‘outside’ with the largest high biocontainment facility ‘inside’ in the southern hemisphere. My work here involves using the PC4 facilities to test my gene silencing molecules against live Hendra virus. After completion of my PhD I would like to continue working on a translational project that has clinical relevance in either industry or academia. My PhD thus far has succeeded due to the treasured support from friends, colleagues and supervisors at UQDI and has allowed me to experience all avenues of science.

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Conferences and Awards: AusBiotech national conference > Winner of QLD GSK AusBiotech student excellence award Australasian virology conference > Australian Society of Microbiology student oral award Infection and Immunity > Nature Immunology first place poster prize > Finalist in the Women in Technology PhD Career Start Award


Alumnus Diwakar Ram Pattabiraman, UQDI Graduate I completed my Bachelor of Science in India at the University of Madras. After completing my science degree, majoring in microbiology, I came to Brisbane to pursue a coursework Masters in Biotechnology at UQ. Realising in the first semester that the research component was not enough for my liking, I changed my program to a Masters by Research (M.Phil). I was always interested in the haematopoietic system and leukaemia and was drawn towards the projects in Professor Gonda’s lab at The University of Queensland Diamantina Institute (UQDI), which was studying the molecular mechanisms of oncogenesis, particularly related to blood disorders. The location of the Institute within the Princess Alexandra Hospital campus also seemed an advantage when working on cancer, due to easier interactions with the clinical side.

Biomedical Research, a part of the Massachusetts Institute of Technology in Cambridge, USA. I now work on solid tumours, mainly breast cancers, to study the mechanisms by which they are able to metastasise to different sites in the body, as this is responsible for over 90% of cancer-related deaths.

During my PhD I worked on a protein called Myb that plays an essential role in the development of the haematopoietic system, responsible for the generation of blood cells in our body. The protein has also been shown to play a role in the development of several cancers of the haematopoietic compartment including myeloid and lymphoid leukaemias. My PhD project entailed studying the biochemistry of the protein and its interacting partners, and defining their role in the transformation of haematopoietic cells that ultimately results in leukaemia.

In the past six years, I have had the opportunity to meet many wonderful people who have helped me at different stages of my PhD. This enabled me to open up my boundaries of technical expertise pick up pieces of wisdom from many people.

I was fortunate to be part of a laboratory that utilised a wide variety of molecular biology and cell biology techniques, genomics, flow cytometry, and mouse work. I believe, more importantly, I was provided the right balance of supervision and independence throughout my program that enabled me to gradually start thinking on my own about my experiments and the direction of my project. I was also provided with ample opportunities to attend several scientific meetings and workshops during my studentship, enabling a more global view of the whole field and where my project fit, allowing me to interact with many local and international scientists in my field. I also learnt the art of scientific writing from Professor Gonda through the multitude of abstracts, chapters and papers for which he patiently provided critique. I am currently a Postdoctoral Research Associate in the laboratory of Professor Robert A. Weinberg at the Whitehead Institute of

My time at UQDI helped me gain proficiency in different laboratory techniques that I use extensively today. One of the main lessons I learnt from my PhD was problem solving and the art of persistence. I believe I will carry these with me through the rest of my career. I was able to get my name on four publications during my time at UQDI; we also currently have one manuscript that is under review and Professor Gonda and I are writing a review article that we hope to submit in 2012.

The most enjoyable aspect of my PhD was learning how to think independently as a scientist. There is a deep satisfaction when you design your own experiment using a model system that you set up, and it actually works! Although you do not experience success on a very regular basis in the lab, it is these scattered events that keep you motivated during the course of a PhD and help you through it. UQDI is a very close-knit Institute where everyone knows everyone, giving the place a lot of warmth. This cordial and friendly atmosphere also helps to keep your spirits up at all times. I really enjoyed being a part of it and have some very good memories from my time there.

Conferences and Awards: > Cancer Council Scholarship > Leukaemia Foundation Scholarship > UQDI Jian Zhou Pre-doctoral Award > Graduate School International Travel Award > ASMR Postgraduate Runner-Up Award 27


Training the next generation 2011 was the third year of operation for Students Performing Advanced Research Queensland (SPARQ-ed), UQDI’s innovative educational outreach facility. Since commencing in 2009, following a proposal to the Queensland Government by Professor Ian Frazer, SPARQ-ed has seen more than 2000 students and 200 teachers participate in its unique research programs and workshops. SPARQ-ed is the result of a partnership between UQDI and Queensland’s Department of Education and Training (DET). Its aim is to engage school students and teachers with the scientific community by putting them in touch with members of UQDI’s world ranked research team. All of SPARQ-ed’s services are developed by the SPARQ-ed Coordinator (Dr Peter Darben, an experienced science teacher employed by DET) in conjunction with UQDI’s research groups. At the core of SPARQ-ed’s offerings is the research immersion program, a five-day intensive science experience for senior school students and their teachers based around a project on the work done by UQDI’s research groups. These projects are designed to provide a result which could potentially contribute to the work completed by the Institute’s research group. The programs are conducted in a dedicated teaching laboratory stocked with all of the equipment necessary to run a modern cell and molecular biology facility, on the grounds of the Princess Alexandra Hospital. UQDI research and higher degree students act as tutors in these programs, ensuring that participants interact with enthusiastic young scientists at the start of their research career. SPARQ-ed also runs a family homestay service through the International School at Kelvin Grove State College which allows students from outside the southeast corner to participate in these unique programs. 2011 saw a rapid increase in interest in the research immersion programs among students, with nine programs based on seven projects conducted from 89 students (and two teachers) from

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32 schools throughout Queensland. This is compared with 86 students in 13 programs from 31 schools for the first two years of the program. Of the 89 students participating in the 2011 programs, 45% came from schools outside the Brisbane metropolitan region (including students from Townsville, Innisfail, Moranbah and Weipa). The number of student participants in these programs is expected to increase in 2012 with the introduction of the SPARQ-ed Bonus Rank Program, which allows students to gain a point under the UQ Bonus Rank Scheme for tertiary entrance. In 2011, SPARQ-ed also expanded the range of services offered, with shorter “Cell and Molecular Biology Experiences” and workshops for upper primary and middle school students. These programs are offered to whole classes and provide an opportunity for students to learn concepts and carry out techniques which are impractical to perform in traditional school settings. Despite targeting these programs at schools in the Brisbane metropolitan area, nearly half of the participating students came from schools outside this region (including schools as far away as Hervey Bay and Stanthorpe). SPARQ-ed also provided much needed professional development for school staff, with workshops delivered on site for teachers and school scientific operations officers, and at professional network conferences. These initiatives saw SPARQ-ed recognised with a 2011 Peter Doherty Award for Excellence in Science Teaching (Science Education Partnership and Community Science division). In the short time since its establishment, SPARQ-ed has proven itself a leader in providing authentic biomedical science experiences for Queensland’s school communities. In 2012, SPARQ-ed will make the move alongside UQDI to custom built facilities in the new TRI, allowing it to continue providing this unique service to more Queensland students and teachers.


SPARQ-ed alumnus experience Passionate about biology and sun safety, Mansfield State High School Grade 12 student and prefect Jeanette Hew, credits the SPARQ-ed program with helping her move closer towards a career in science. Introduced to the program by the Head of Science at Mansfield State High School, Jeanette was encouraged to apply to SPARQ-ed, having shown great strengths in her science studies at school, and an ambition to gain exposure into tangible medical research with real-life outcomes. Jeanette studied a week-long intensive program on cell proliferation and CHK2 inhibition as part of the UQDI melanoma research project with Associate Professor Brian Gabrielli and PhD student, Kelly Brooks. “I wanted to see if biomedical science was what I was really interested in studying, so the SPARQ-ed program seemed a wonderful opportunity for me,” she says. Jeanette first discovered her love of science learning the subject not in English, but impressively, in French. As part of the Mansfield State High School French immersion program, Jeanette completed multiple subjects in the language from Year 8, however science really piqued her intrigue. “Science is a language of life for me - so many aspects of life revolve around science and the discoveries behind it,” she says. “I found the SPARQ-ed program greatly helped with my school studies, my expression work and with my report writing abilities. My teacher even commented on how much I’d improved after I’d attended the program.” Mr James Sloman, Principal of Mansfield SHS, says “SPARQ-ed provides high performing students to engage in rich, high-quality learning experiences. This compels them to grapple with advanced research questions.” Jeanette’s keen interest in science and participation in the SPARQ-ed program has given her a much clearer understanding of diseases and how they occur, and the severity of melanoma, particularly in Queensland. Having enjoyed the week-long intensive program so much and having become increasingly passionate about sun awareness as

SPARQ-ed Student: Jeanette Hew a result, Jeanette even organised for Associate Professor Brian Gabrielli to present a session about sun safety and the dangers of melanoma to her school. Jeanette, as part of her prefect team, is also working with her Principal and her peers to reinforce the importance of the school hat to encourage better sun safety awareness. But Jeanette also has interests in other areas of science. She wants to become an obstetrician after school, and is hopeful even despite her busy schedule in senior year, she will be able to apply for a second SPARQ-ed program in 2012 to gain further exposure into UQDI’s research. “Science is the bridge to the unknown. It’s something which can unravel much about the world,” Jeanette says. “Spreading the love of science is a cure in itself; to show people what can be achieved through research and get them involved to help make a change.s”

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Senior Researchers

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Dr Antje Blumenthal. Research Group: Alan Yu Research Assistant, Marcela Gatica Andrades PhD Student, Andreas Puyskens Honours Student, Tegan Henderson Undergraduate Student, Jiang Zhu Undergraduate Student, Lee-Anna Burgess Visiting Medical Student, Kelly Hitchens Visiting PhD Student

If we understand how microbes make us sick and which immune responses are required to combat infection, we can hopefully develop successful vaccines and treatments for diseases that we are still battling. We live in times of increased international mobility where infectious diseases pose global challenges and are not necessarily restricted by geographical borders.

Dr Antje Blumenthal Infectious diseases remain a major threat to public health worldwide and cause severe morbidity and mortality. Dr Antje Blumenthal investigates how pathogens are recognised by immune cells and how this alerts immune mechanisms that can successfully control the infection. One of her main interests is tuberculosis. The World Health Organisation estimates that one third of the people worldwide are infected with Mycobacterium tuberculosis, the bacterium that causes tuberculosis, and one in ten infected will develop the disease within their lifetime. While treatment is complex and lengthy, tuberculosis is a curable disease. Yet it still kills 1.7 million people every year - about 4,700 people everyday. Most people who die from tuberculosis today live in the developing world. However, several areas of the world have seen a recent rise in cases resistant to many, or all, currently available tuberculosis drugs. These drug-resistant strains have now added a major concern to this public health threat and emphasise that an effective vaccine and novel drugs are needed. Dr Blumenthal’s team focuses on how the immune system identifies, responds to and controls infections. Her particular interest lies in the immune defence against Mycobacterium tuberculosis. Macrophages are specialised immune cells that engulf and kill pathogens and alert further immune cells to mount effective immune responses. Mycobacterium tuberculosis has developed mechanisms to survive within these cells, often throughout the lifetime of the host. A network of immune cells has to collaborate effectively to contain the infection and avoid the development of active disease. Macrophages play a central role in initiating and regulating these responses. Dr Blumenthal’s studies have revealed a new part of the sensor complex on macrophages that recognises mycobacteria. It was found that this sensor helps control lung pathology in a model of tuberculosis. Current studies focus on mechanisms as to how this pathogen sensor contributes to immune responses to Mycobacterium tuberculosis. While optimal initiation of immune responses is important to control infections, balancing effective anti-microbial

responses with regulatory mechanisms that control inflammation and prevent tissue damage is essential. Thus, Dr Blumenthal’s team is investigating how a novel class of immune regulatory molecules regulates macrophage functions during infection. This emerging research field will improve fundamental understanding of how immune responses are controlled and might identify novel indicators and treatment strategies for severe infections and chronic diseases. Current research projects: Innate immune recognition of pathogenic mycobacteria Macrophages are the major host cell for Mycobacterium tuberculosis, the bacterium that causes tuberculosis. We are investigating how macrophages recognise Mycobacterium tuberculosis and initiate these immune responses to control the infection. Our interest is focused on how pathogen sensors on the surface of macrophages signal presence of the bacterium to the host cell and how this is translated into alert mechanisms that communicate the infection to other immune cells. Regulators of inflammation Many of the immune mechanisms that help control pathogens can also be harmful to the surrounding host cells. Therefore, tight control mechanisms are needed to prevent tissue damage and chronic inflammation. The team are studying mechanisms that balance effective immune control of pathogens and inflammation. This research will improve understanding of general mechanisms underlying immune responses and might inform novel strategies to manage severe infections and chronic diseases. Identification of novel antimicrobials The emergence of Mycobacterium tuberculosis strains that are resistant to current drugs has added additional concerns about this global health problem. Dr Blumenthal is searching for novel antimicrobials that might have the potential to become new drugs in the global battle against tuberculosis.

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Professor Matthew Brown. Research Group: Adrian Cortes PhD Student, Aideen McInerney-Leo Genetics Co-ordinator, Brooke Gardiner Senior Research Officer, Emma Duncan Senior Research Officer, Eugene Lau Research Assistant, Gethin Thomas Research Fellow, Graeme Clark Postdoctoral Scientist, Hsu-Wen Tseng PhD Student, Janelle McFarlane Research Nurse, Jessica Harris Research Assistant, Johanna Hadler Research Assistant, Karena Pryce Research Technician, Katelin Haynes Honours Student, Katie Cremin Research Assistant, Kelly Hollis Research Nurse, Kim Gardner Administrative Officer, Linda Bradbury Research Nurse Marina Donskoi Research Assistant Mary-Ellen Costello PhD Student Mhairi Marshall Bioinformatician Paul Leo Senior Bioinformatician Philip Robinson PhD Student Poh-Lynn Low Research Assistant, Sharon Song Research Assistant, Stuart Davidson PhD Student, Tony Kenna Research Fellow

As a clinician who cares for patients with the diseases I research, I see in my clinics first-hand the need for better treatments for these conditions. Discoveries my group has and is making will change the lives of hundreds of thousands of people for the better.

Professor Matthew Brown Ankylosing spondylitis affects approximately 100,000 Australians; currently there are no treatments available which induce remission in the disease or improve its natural history.

> Investigating and developing treatments for ankylosing spondylitis targeting genes or pathways identified by our genetic studies, with the goal of inducing disease remission

The Brown Group investigates a wide range of common and rare genetic disorders, focussing mainly on bone and joint diseases such as ankylosing spondylitis and osteoporosis. Identifying genes that cause these diseases informs research into how the diseases are caused, and thus potential ways of treating or preventing disease.

> Understanding how inflammation in ankylosing spondylitis induces bone formation across joints, and investigating ways of prevention

The team is the leading group internationally in research into the disease ankylosing spondylitis, and have played a major role in the identification of all thirteen genes discovered in the disease since 1972. These discoveries have changed the direction of ankylosing spondylitis research globally and led to the development of new, effective treatments for the condition. Current research projects: > Mapping genes involved in common bone and joint diseases including ankylosing spondylitis, osteoporosis and rheumatoid arthritis

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> Determining how genes in the IL-23 pathway influence the risk of AS. > Mapping genes involved in common neurological conditions including multiple sclerosis, motor neurone disease, schizophrenia and intracranial haemorrhage > Mapping genes influencing the risk of tuberculosis > Mapping genes in common ophthalmological conditions including diabetic retinopathy and glaucoma > Developing sequencing-based methods for rapidly identifying genetic mutations in rare human diseases, focussing on skeletal dysplasias


Dr Marcel Dinger. Research Group: Joanna Crawford Research Officer, Dennis Gascoigne PhD Student

Nature has provided every living organism on Earth with an instruction manual for its development and function. If we can understand how to read it, we can understand how to fix it when things go wrong.

Dr Marcel Dinger The genome contains all the information necessary to guide the development of a single-celled embryo to an adult. In turn many diseases, including all familial diseases and most types of cancer, result from mutations in the genome sequence. However, the function of only a tiny proportion of the human genome is known. Genome sequencing has enormous potential to transform our understanding of disease and revolutionise its treatment. Dr Dinger’s research interests lie in understanding the functions of those regions of the genome that lie outside of genes that encode proteins. Such so-called noncoding DNA was traditionally considered as evolutionary remnants, but have recently been found to be transcribed into RNA. Dr Dinger played an instrumental role in demonstrating that these RNAs were transcribed in a remarkably specific manner during development as well as across adult tissues and specific cell types and were therefore likely to be generally functional. Dr Dinger developed the first commercial microarray to detect the expression of noncoding RNAs, which led to the profiling of these novel molecules in many different developmental models and diseases. The investigation of noncoding RNAs in melanoma and breast cancer each led to the identification of novel genes involved in the aetiology of these diseases, presenting opportunities for development of new treatments.

Dr Dinger’s current research harnesses the power of next-generation sequencing to understand the relationship between the transcriptional output of the genome and disease. His main focus lies in unraveling the perturbations in the transcriptome that occur during the early stages of melanoma. Current research projects: > Functional characterisation of the regulatory architecture of melanoma-associated loci > Identification of novel long noncoding RNAs in skin cancer by whole transcriptome sequencing > Investigating the role of viruses in squamous cell carcinoma by genomic and transcriptomic sequencing > Translation of next generation sequencing technology for clinical diagnostic and prognostic applications > Application of personal and skin cancer genome sequencing for guiding treatment and modifying lifestyle

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Professor Ian Frazer. Research Group: Sunny Liu Research Officer, Janin Hoffmann Postdoctoral Research Fellow, Antje Blumenthal UQ Postdoctoral Research Fellow, James Wells Research Fellow, Graham Leggatt Research Fellow, Purnima Bhat UQ Postdoctoral Research Fellow, Deepak Mittal Research Officer, Anne-Sophie Bergot Research Officer, Oscar Haigh Research Officer, Stephen Mattarollo Balzan Fellow, Marcela Gatica Andrades PhD Student, Kelly Hitchens, Christina Gosmann PhD Student, Alan Yu Research Assistant, Le Son Tran PhD Student, Ajit Shukla, Andreas Puyskens Visiting Student, Lee-Anna Burgess, Jennifer Bridge Research Assistant, Allison Choyce Lab Manager, Stacey Cole Lab Manager, Rohit Sinha Research Assistant, Michelle Yong Research Assistant, Shanu Sinha Research Technician, Tracy Doan Casual Research Assistant

I am a clinician, and I want my research to help those who are sick, and to help prevent disease. I see the anxiety that results from a diagnosis of cancer, and research is what gives cancer sufferers hope.

Professor Ian Frazer Cancer is now the commonest cause of death in Australia, and one in two of us will develop cancer in our lifetime. We need to understand how our immune system sees cancer cells as non-self, which we can demonstrate through the antibodies patients with cancer develop to their own cancers, but nevertheless fails to eliminate cancer tissue like it eliminates viruses infected cells. Professor Frazer and his group study how the environment of cancer cells determines whether the immune system, and anti-cancer vaccines, can induce killer T cells that can kill cancer cells. The answer lies in the inflammatory response that is induced by abnormal cancer cells. Frazer’s animal models show that manipulation of local inflammation turns an ineffective immune response into an effective one. The next steps are to learn how to safely do this in patients with cancer. Focussing on the cells that sense distressed and abnormal cells, as these cells seem able to direct the behaviour of the tumour specific killer cells. A rather esoteric sensor cell, the NKT cell, which is naturally present in the environment of tumours, plays a central role in deciding what message to send to tumour-specific killer cells, but what instructs the NKT cell to sending a positive or a negative signal to the killer cells? The aim is to bypass a negative signal from these cells, to overcome the inhibition of killer T cells and allow tumour destruction. Current research projects: How killer T cells kill skin cancer cells Killer T cells (CD8 cells) are present in large numbers in an activated state in early virus infections in skin and help to clear infection. Killer T cells are also found in early cervical cancers, where they appear to be ineffective in eradicating disease. Mechanisms used by CD8 T cells to kill skin cells expressing HPV tumour antigen are being examined by Dr Purnima Bhat, using live tissue imaging with time-lapse microscopy and in vivo imaging with multi-photon microscopy. Mechanisms of local immunosuppression induced by cancers Infection has been associated with approximately one in five human cancers worldwide, and particularly with epithelial cancers. Breaking immune tolerance against infected or cancerous tissue is a challenge for the development of effective cancer immunotherapy. The Frazer group are studying the factors that are involved in local

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immunosuppression in HPV infection. Using animal models, the group’s research mimics the precancers caused by this infection. IFN- inducible immunoregulatory pathways that may inhibit immune effector responses to HPV16-E7 are being studied by Dr Deepak Mittal and student Son Tran-Le. Student Christina Gosmann is studying ineffective skin inflammation induced by chronic viral infections regulated by the inflammasome. She is also looking into how a sensor system responding to dead and dying cells can activate a sentinel cell of the immune system (an NKT cell) to stop local killer T cell functions. The role of regulatory T cells and mast cells in signalling killer T cells not to kill cancer cells, is being studied by Dr Anne-Sophie Bergot. Delivering therapies to overcome local immunosuppression Soluble signalling molecules are produced from virus infected skin and regulate the immune response to viruses and cancer. The group wish to eliminate this signalling using siRNA as an inhibitor. Delivery of siRNA as an inhibitor ian nhibitor of local immune suppression by a novel nanoneedlesystem developed by collaborator Professor Mark Kendall is being tested by Dr Oscar Haigh as a potential therapy to treat skin cancers. Overcoming suppression by creating local inflammation is being tested in clinical trials in collaboration with Dr David Jardine at the Princess Alexandra Hospital and his colleagues. Approaches to elimination of cervical cancer in the developing world Recognition that cervical cancer is promoted by infection with human papillomavirus has led to the development of vaccines to prevent cervical cancer, and virus specific tests to detect the early stages of cervical cancer. We have evaluated the feasibility of using a combination of vaccination and screening for HPV infection as a means to control cervical cancer in the developing world, where cervical cancer is a common cause of death. Studies in Vanuatu have shown that HPV vaccination programs run by local agencies are feasible and acceptable with >90% uptake amongst eligible school children. Studies undertaken with Dr Silvia Francesci at International Agency for Research on Cancer and Dr Julia Bretherton in Melbourne have demonstrated that testing for HPV infection in women over 30 in Vanuatu is effective for identifying women at risk of developing cervical cancer, who can then be treated.


Associate Professor Brian Gabrielli. Research Group: Sandra Pavey Senior Postdoctoral Research, Alex Pinder Research Assistant, Kelly Brooks PhD student, Mellissa Brown PhD student, Won Jae Lee CJ Martin Fellow, Kee Ming Chia Research Assistant, Vanessa Oakes PhD student, Matthew Wigan PhD Student, Tanya Pike, PhD Student, Robyn Warrener PhD Student

We are only just starting to understand how we can use the defects responsible for tumour formation as targets to selectively destroy the tumours.

Associate Professor Brian Gabrielli Melanoma is a disease that affects almost every family in Australia, yet there are few effective treatments available. The debilitating side effects of conventional chemotherapeutics are a direct consequence of their poor targeting, destroying normal tissue as well as cancer. Improved targeting of the cancer by zoning in on a defect that is specific for the cancer will improve both treatment outcomes and reduce side effects, thereby improving the quality of life of the patient. Associate Professor Gabrielli’s Cell Cycle Group is investigating the normal response to skin cells of environmental and other stresses, identifying the molecular basis of defects in these response mechanisms and attempting to use these defective mechanisms as selective targets to destroy melanomas. The team have found several stress response mechanisms that are defective in melanomas and have now shown that targeting these provides the selective targeting desired to improve treatment options and reduce side effects for patients. Current research projects: There are two themes to the group’s research program: examining normal cell proliferative controls and how they go wrong in cancer, and targeting these defective controls to selectively destroy cancer cells with these defects. In the first theme there are two projects: Defining the molecular mechanism of the cell cycle response to ultraviolet (UV) radiation; understanding the molecular nature of the defective checkpoint signalling in melanoma. These projects examine mechanisms that contribute to regulating normal cell

division in the face of environmental stresses such as UV radiation and imposed stresses such as chemotherapeutic agents. We have identified a mechanism by which skin cells recognise and respond to all of the DNA damage caused by UV exposure, and shown that this mechanism is defective in a high proportion of melanomas. The Gabrielli group has identified another mechanism that responds to chemotherapeutic drugs is also commonly defective in melanomas. The former defect appears to directly contribute to melanoma development semicolon; the latter may account for the resistance of melanomas semicolon; to standard chemotherapeutic treatments. The second theme is based on utilising our understanding of the defects in these stress responses to develop improved targeted anticancer drugs. The group has shown that inhibiting one component of a stress response, Chk1, provide selective cytotoxicity in melanoma and identified a marker of sensitivity to this targeted therapy, a critical adjunct as it provides a means of identifying tumours most likely to be sensitive to this drug. Gabrielli and his team have also been investigating means of selectively targeting melanomas that are defective for the response to standard chemotherapeutics. The team have used a novel approach to do this, knocking out one gene at a time in melanomas to identify genes that when knocked out combine with the defective chemotherapy response to selectively kill cells with the defective response. This is termed a “synthetic lethality” screen and is possible due to the unique functional genomics facility that have been established at The University of Queensland Diamantina Institute.

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Professor Tom Gonda. Research Group: Ping Ye Research Officer, Partha Mitra Senior Research Officer, Crystal McGirr Research Assistant, Duka Skalamera Research Officer, Mareike Dahmer Research Assistant, Diwakar Pattabiraman PhD student, Clement Kiu Research Assistant, Konstantin Shakhbazov Research Officer

I believe that a thorough understanding of the genetic, cellular and molecular basis of cancer holds the key to new treatments. But these treatments won’t just appear - we have to think about how our discoveries can be exploited to make them happen.

Professor Tom Gonda There have been some spectacular successes in cancer treatment with molecular-targeted therapies over the past two decades; however the lack of such therapies for many cancer types remains as a major gap in our arsenal. The transition from a normal cell to a cancer cell is driven by changes to genes that either promote or suppress cancerous properties such as uncontrolled growth, invasion of adjacent tissues etc. These two classes of genes, called oncogenes and tumour suppressor genes, respectively, represent potential targets for cancer therapy. That is, we can try to develop drugs that “hone in” and block the cancer-promoting actions of these genes. In particular, cancer cells are often “addicted” to oncogenes in being more sensitive to their loss than non-cancerous cells. Thus, identifying oncogenes that are important for particular cancer types and subtypes is a critical first step in developing potential new treatments for these diseases. Research in Professor Gonda’s Molecular Oncogenesis Group can be divided roughly into two areas. The first focuses on an oncogene called MYB that is already known, through the group’s work and that of others, to be several important human cancers - leukaemia, breast cancer and bowel cancer. The group is trying to understand how it promotes cell growth and blocks normal cell maturation. The Gonda lab is also working on approaches for targeting MYB that can be developed, either singularly or in combination with other drugs, as possible cancer treatments. The second part of this work aims to identify new targets for cancer treatment. One major effort in this direction, which goes by the acronym “ARVEC”, is to develop novel technology to test large numbers of genes for their ability to confer or block properties important for cancer cell function.

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Current research projects: Role and targeting of the interaction between Myb and p300 in myeloid leukaemia Having found that this interaction is critical for both MYB’s own ability to convert normal haemopoietic (blood-forming) cells to leukaemia-like cells, the group has now turned their attention to Myb’s role, and that of its interaction with p300, in allowing or aiding leukaemia caused by other genes. Research funded by two NHMRC grants awarded for 2012-14 will identify which genes are important in this latter facet of MYB’s function, and how we can target the interaction to suppress the growth of leukaemia cells. Control of MYB expression by transcriptional elongation The MYB gene is turned on and off by a somewhat unusual mechanism. Transcription is initiated in almost all situations but elongation of the RNA transcript is subsequently blocked in cases where no mature MYB mRNA is present, i.e. when the gene is “off”. The Gonda group are studying how this block is overcome and exploring whether reimposition of the block could be used to suppress MYB, and hence cancer cell growth in MYB-dependent cancers. Enhancing the effects of MYB inhibition on cancer cell growth with new drugs The team previously found that suppression of MYB expression (MYB knockdown) in breast cancer cells prevents growth but does not actually kill the cancer cells. However, they also found that combining MYB knockdown with certain compounds enhanced the effect and led to extensive cancer cell death. The Gonda group are pursuing these findings in breast cancer using agents that could be advanced to clinical application, and extending this potential therapeutic approach to leukaemia.


Dr Michelle Hill. Research Group: Kerry Inder Research Officer, Debra Black Research Assistant, Dorothy Loo Proteomics Specialist, April Choi PhD Student, Sunny Moon PhD student, Lara Petelin Honours student, Caroline O’Leary Casual Research Officer, Hien Nguyen Causal Research Assistant, Jayde Ruelcke Causal Research Assistant

I believe an interdisciplinary approach is necessary to progress medical research. I hope to lead my multi-disciplinary team to make discoveries that will help cancer patients and their families.

Dr Michelle Hill Every second Australian will be diagnosed with cancer in their lifetime. Even after treatment, the threat of relapse stays with cancer survivors and their families.

Caveolin, PTRF and cholesterol-rich lipid raft domains in prostate cancer

Current research projects:

High blood cholesterol is associated with advanced prostate cancer, and use of cholesterol-lowering statin therapy has been associated with reduced risk of advanced prostate cancer. The group has been investigating the role of cholesterol-binding protein, caveolin -1, and its co-factor PTRF (Polymerase I and Transcript Release Factor, also called cavin-1) in prostate cancer. The initial results led to the hypothesis that caveolin and PTRF expression modulates the tumour microenvironment by altering the lipid raft content leading to altered protein secretion, including microvesicles/exosomes. Excitingly, PTRF expression in an aggressive prostate cancer cell model reduced the release of the pro-cancer molecules from the cell, concomitant with reduced oncogenic properties in vitro. We are in the process of testing these results in an in vivo model.

Glycoprotein biomarker discovery pipeline

Canine haemangiosarcoma diagnostic test

The Hill group has been developing a pipeline for the discovery of serum glycoproteins that can be diagnostic of diseases such as cancer. Glycoproteins are proteins with sugars added to their side chains during their production. Changes in the sugar side chain structure of glycoproteins have been found during cancer development and progression. To find these changes in blood glycoproteins, they have developed a novel lectin magnetic bead array-coupled mass spectrometry (LEMBA) method, as well as a database with data mining tools called GlycoSelect (with collaborators Dr David Chen and Dr Kim-Anh Le Cao). The team are now using this pipeline to discover blood biomarkers in cancers.

Haemangiosarcoma, cancer of the cells that line the blood vessels, is very common in certain breeds of large dogs. Due to the high rate of recurrence and the lack of a rapid diagnostic test, dogs with suspected spleen rupture (abdominal bleeding) are often euthanased. A rapid clinical diagnostic test is urgently needed to avoid euthanasia of dogs that have other curable diseases. Using LeMBA and GlycoSelect, Hill’s group have obtained a list of altered glycoproteins in the serum of dogs with haemangiosarcoma, in collaboration with The UQ School of Veterinary Science, and partly supported by the Australian Animal Cancer Foundation. Work is underway to validate these markers.

Prostate cancer progression/recurrence test

A similar cancer exists in humans called angiosarcoma. Angiosarcoma is quite rare but deadly, hence their results in dogs may provide useful lead biomarkers for further confirmation in human patients where sufficient cases may not be available for extensive study.

Cancer death can be reduced by early diagnosis and/or more effective therapies. Dr Michelle Hill’s team are working to discover 1) new blood markers that can be used for cancer screening or to predict therapeutic efficacy (personalised medicine), and 2) new drug targets for cancer therapy by stopping the pro-tumour tissue environment. Dr Hill’s research interest lies in the development, use and clinical translation of diagnostics and therapeutic targets with a major focus in cancer. Her multi-disciplinary team is leading the field with pioneering proteomics and systems biology methods for the discovery of cancer biomarkers and therapy targets.

Prostate cancer is the most commonly diagnosed cancer, and the second leading cause of cancer death in Australian men. Localised prostate cancer can be effectively treated but recurrence, accompanied by metastasis (spreading to other organs) is currently incurable. On the other hand, prostate cancer is a slow growing cancer and many patients may not require active treatment in their lifetime. Working with the Australian Prostate Cancer BioResource and Dr Margot Lehman at the Princess Alexandra Hospital, they are using a two-pronged approach to identify serum biomarkers that can indicate or predict prostate cancer spreading. Glycoprotein changes in serum proteins are screened using LeMBA and GlycoSelect technology, while tiny vesicles secreted by cancer cells, are isolated and their protein, lipid and RNA content profiled.

Mass spectrometry-based amyloidosis subtyping Amyloidosis is a group of conditions in which abnormal proteins aggregate in the blood and can cause organ failure. Diagnosis involves staining for protein deposits in biopsies. Identification of the protein causing the amyloidosis is required to guide clinical decisions, however, current histological methods are unable to provide positive identification in many cases. The Hill group are working with Pathology Queensland clinical researchers at the Princess Alexandra Hospital to establish a mass spectrometry-based method for amyloidosis subtyping.

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Dr Graham Leggatt. Research Group: Michelle Yong Research Assistant, Andrew Kassianos Postdoctoral Fellow, Lisel Nicols Undergraduate Student

I believe that good basic science in understanding how the immune system interacts with skin cancer will underpin new immunotherapies for the clinic.

Dr Graham Leggatt Non melanoma skin cancers are very common in Queensland and a subset of these cancers are aggressive and prone to metastasis. Current treatment for the primary tumour most commonly involves surgical excision which can be disfiguring. The Leggatt group aim is to improve treatment options by promoting immune attack against the developing cancer. Enhancing the immune attack generally involves the removal of suppressive cells and mechanisms that locally surround the tumour. The team have begun to identify these suppressive circuits and how to overcome their effects. The Leggatt group works on immunotherapy for non-melanoma skin cancers and HPV-related epithelial cancers. In particular, their aim is to enhance the function of cytotoxic T cells, a key immune cell in our defence against tumours and viruses, at skin cancer sites. The group has identified key suppressive mechanisms which prevent immune attack by cytotoxic T cells during early stage cancers in the skin. In particular, natural killer T cells are attracted to precancers in the skin where they secrete IFN-g and switch off the local immune response. They are actively identifying the target cells influenced by IFN-g in the skin in an attempt to deplete or neutralise their suppressive effects. These preclinical findings provide potential target cells and molecules which need to be

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eliminated within the skin of cancer patients in order to restore anti-tumour immunity. Recently, Leggatt’s group has successfully depleted suppressive cells from skin precancers in mice and restored anti-tumour immunity. This finding will be further pursued in mice to determine the best path toward a therapy in human patients. Other projects have focused on how lymphocytes accumulate within precancerous tissue. Using mice which transgenically express the E7 cancer forming protein of HPV, Leggatt has found key chemical messages released from the skin, chemokines, which attract a variety of lymphocytes into the skin. If the team can identify the key chemokines which attract suppressive lymphocytes to the precancerous skin, it may be possible to block this traffic and restore the anti-tumour immune response. Current research projects: 1. T cell trafficking to precancerous skin 2. Adoptive immunotherapy of squamous cell carcinoma after depletion of lymphocytes 3. IFN-g induced immunosuppression within precancerous skin 4. Suppressive dendritic cell subsets in precancerous skin


Associate Professor Nigel McMillan. Research Group: Liz Payne Research Assistant, Lisa Putral Research Officer, Sarina Cameron Research Assistant, Melinda Burgess Research Assistant, Stephen Blake UQ Postdoctoral Research Fellow, Oscar Haig Research Officer, Fawzi Bokhari PhD Student, Jana McCaskill PhD Student, Richa Singhania PhD Student

As Carl Sagan, the American cosmologist said - “Somewhere, something incredible is waiting to be known”. This is the excitement I bring with me to work each day, wondering what new discoveries await and how we can improve the lives of patients.

Associate Professor Nigel McMillan We are reaching the limits of what conventional cancer treatments can achieve and we clearly need new approaches to improve patient outcomes. This will require us to move into an age of gene-based medicines and treatments based on controlling the very genes that cause cancer. Only in this way will we be truly manage to prevent, control, treat and cure these diseases. We know cancer is caused by mutated or lost genes. We now have the ability to turn off single genes within a cell using a technology called gene silencing and we are pioneers of using this technology. We need to understand how to make this technology work at a practical level as well as understand the underlying biology of such therapies and bring them into play the immune system - the ultimate cancer cure. Associate Professor McMillan and his group study how gene silencing works as a means to killing cancer cells. His team and their collaborators take a multidisciplinary approach to their work, combining the skills of pharmacists, nanotechnologists, biologists, virologists and immunologists to address the issues. In order for gene silencing to become a reality in the clinic, the practical issue as to how to deliver the treatment to the cancer cells is yet to be solved. The team have developed a number of delivery technologies that look promising in animal models and these will soon be tested in humans, provided this can be done safely. The team is also investigating the fundamental biology of gene silencing and have made startling new findings that will alter the entire field. Such findings have implications for better treatments. Finally, the team is using their expertise to address how we might use gene silencing to treat some of the worst infectious viral diseases such as RSV, Hendra virus and a range of other respiratory diseases that devastate both young and old.

Current research projects: Gene silencing as a cancer treatment The McMillan group’s work focuses much of its efforts on developing gene silencing methods in the treatment of cancer. They are interested in developing practical ways to implement this new technology in humans and also to improve the therapy by causing the immune system to now “see” the cancer. This sort of dual activity makes this treatment potentially much more effective as even untreated cancer cells will be killed. The team has developed a range of new delivery technologies from new “dendrimers” with our collaborator Professor Michael Monteiro, to new microfibre-based methods with Dr Tarl Prow and nanoneedles for skin delivery with Professor Mark Kendall. The group has also developed novel systems to successfully deliver siRNA to the vaginal tract, a first step in human clinical trials for cervical cancer. They are currently working on developing trials and treatments for cervical cancer, melanoma and a range of viral infections. Chronic Lymphocytic Leukaemia (CLL) CLL is the most common adult leukaemia but current treatments only reduce disease burden and there is no cure. In collaboration with haemotologists at the Princess Alexandra Hospital the McMillan group has been working on ways to investigate novel treatments for CLL. They have discovered that this cancer depends on a particular protein and that treating cells in the test tube with antibodies to this protein causes them to die. The team are developing these antibodies as a new therapy for CLL.

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Dr Ali Naderi. Michelle Meyer Research Assistant

As a physician-scientist, my aim is to find better treatments for cancer patients.

Dr Ali Naderi Breast cancer is the most common malignancy in women, accounting for 25% of all cases, and is the most common cause of cancer-related mortality in women worldwide.

Current research projects:

Advanced breast cancer is not curable. Notably, there are limited therapeutic options available for a subtype of breast cancer called Oestrogen Receptor-negative disease. This subgroup affects a younger patient population and generally has an aggressive course. Dr Naderi’s research is focused on better understating breast cancer biology, particularly in the case of Oestrogen Receptornegative tumours, and to identify better treatments for this disease.

This project investigates a subtype of breast cancer that is characterised by the lack of oestrogen receptor and the presence of androgen receptor. Currently there are very limited options for the treatment of this subtype of breast cancer. Therefore the results can lead to the discovery of better treatments for this disease. In 2011, the Naderi group successfully characterised a novel signalling pathway with therapeutic implications in this subtype of breast cancer and published two manuscripts on this project.

Dr Naderi has discovered a novel feedback loop between androgen receptor and ERK signalling pathways in this subtype. He has demonstrated a synergistic combination therapy targeting this feedback loop has promising therapeutic potentials in pre-clinical models.

The Study of Novel Signalling Pathways in Molecular Apocrine Breast Cancer

The Study of BEX2 Pathway in Breast Cancer. This project is investigating a novel breast cancer gene, BEX2, that is highly expressed in a subset of breast tumours. Dr Ali Naderi is currently exploring the functional significance of this gene in the biology of breast cancer. In 2011, Dr Naderi published one manuscript on this project.

Fold-change in tumor volume

A.

B.

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6

FLU

FLU + PD

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Synergy between AR and MEK inhibitors in mice xenogrft model of ER-negative breast cancer

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Nuclear expression of BEX2 in a breast tumor (20x)


Associate Professor Nicholas Saunders. Research Group: Liliana Endo-Munoz Senior Research Officer, Andrew Cumming Laboratory Manager, Lilia Merida deLong Research Assistant, Crystal Chang Research Assistant, Orla Gannon PhD student, Sarina Cameron PhD Student, Mehlika Hazar-Rethinam PhD Student

I believe that biomedical researchers must take responsibility for translating the findings from their basic research into improved treatments for patients. This requires them to extend themselves outside the laboratory to become involved in the conduct of clinical trials.

Associate Professor Nicholas Saunders Associate Professor Saunders laboratory focuses on the development and trial of new therapies for the treatment of squamous cell carcinoma and osteosarcoma. Most cancers can be cured by surgery or radiation therapy when detected early. In contrast, advanced or metastatic cancers that have spread to other sites of the body are unlikely to be cured by surgery and radiation therapy. These cancers are therefore more difficult to cure and are frequently associated with patient death. To improve cure rates we need to develop drug therapies that can target disseminated disease specifically. Associate Professor Nick Saundersâ&#x20AC;&#x2122; laboratory is focused on the development of novel targeted drug therapies that can selectively kill advanced cancers. Squamous Cell Carcinoma (SCC): Associate Professor Nick Saundersâ&#x20AC;&#x2122; research group is the first to show that E2F7 is selectively disrupted in human SCC. E2F7 is important in modulating responses to UV and hence this finding informs us how SCC forms and will assist identifying a novel therapeutic target. Osteosarcoma: Associate Professor Nick Saundersâ&#x20AC;&#x2122; team has identified novel genes associated with osteosarcoma metastasis and is now pursuing them as therapeutic targets. Current research projects: Development of novel therapies for cutaneous and oral squamous cell carcinoma Squamous differentiation occurs in the external lining of the skin or the lining of the mouth, nose and throat. In normal states this process of differentiation is tightly regulated. However, in squamous cell carcinomas, the cells of the lining (keratinocytes) have become disrupted such that they no longer control growth, differentiation

or cell death appropriately. Over the past few years Associate Professor Saunders has demonstrated that a key controller of differentiation in normal keratinocytes is the E2F factors. The team have also shown these factors are disrupted in squamous cell carcinomas. Significantly, if they reinstate normal control of the E2F factors in squamous cell carcinoma cells it reinstates normal differentiation mechanisms. These experiments have proved that the E2F factors are a valid target in squamous cell carcinomas. The group is currently developing the E2Fs as potential drug targets in the laboratory and will start in vivo tests of their potential as an anticancer target. They recently completed their first trial in patients of an agent that showed some potential as an anti-E2F drug. Identifying the biological basis for osteosarcoma metastasis Osteosarcoma is the most common primary bone cancer in children and adolescents. Patients who do not have evidence of lung metastases have approximately an 80% chance of being cured. In contrast, those patients who have evidence of lung metastases have only a 20% chance of cure. If one wants to improve cure rates for this disease (currently approximately 50% overall) then it will be important to develop selective cures or preventives for metastatic lung disease. The group has completed a study of patient samples and have discovered that those patients who will develop lung metastases have also lost a particular cell type (osteoclast) in the bone where the cancer arises. The team has now shown that the loss of the osteoclasts is a contributing factor in the causation of lung metastases. Associate Professor Saunders will now conducting laboratory and in vivo tests of potential therapeutics that may prevent the loss of osteoclasts and hence prevent the development of lung metastases.

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Dr Fiona Simpson. Research Group: Shannon Joseph Postdoctoral Research Fellow, Daniel Gaffney Masters student, Lingbo Hu PhD student, Cheryl Lee Honours student, Mallory King Research Assistant

I have recently moved from basic research into more clinical/translational research. I have lost family members to cancer, including my mother. I see the patients we have here in the hospital and I see the worried look on the faces of their families That both inspires me to get the problems fixed and keeps me working hard.

Dr Fiona Simpson Non-melanoma skin cancer (NMSC) is the most common malignancy worldwide and a consequence of chronic exposure to UV. The sun-exposed head and neck is the most common site (70-80%) for the development of NMSC. Australia has the highest incidence of NMSC in the world, with over 300,000 patients diagnosed with cutaneous non-melanoma cancer in Australia per year. 5% of these patients die annually from the consequences of advanced cutaneous squamous cell carcinoma (SCC). Medicare statistics show expenditure on SCC increased in real terms by 24% from 1994 to 2002. SCC is the greatest cost of cancer in Australia at $345 million/year. Early stage SCC is frequently cured by local therapy with surgery, radiotherapy or both combined. Advanced disease is treated aggressively as local control of tumours helps to prevent distressing disruption of organs responsible for speech, swallowing and hearing. There is a need for well tolerated treatments capable of securing control in patients with advanced disease and those not suitable for aggressive therapy. Preclinical and clinical data show that targeting the epidermal growth factor receptor (EGFR), which is over-expressed in 80% of SCC, improves clinical outcomes. Patients treated with anti-EGFR monoclonal antibodies, such as Cetuximab, show improved rates of control and survival, the first such improvement in nearly 20 years. However, not all patients respond and some become resistant to treatment. Given that the anti-EGFR therapies also have associated side-effects, Dr Fiona Simpsonâ&#x20AC;&#x2122;s research is directed towards finding a way to predict which patients will respond to treatment, why some patients do not respond and altering the mechanism of resistance to make the SCCs responsive to the treatments. Dr Simpsonâ&#x20AC;&#x2122;s group is interested in the changes in EGFR trafficking when the receptor is over-expressed in epithelial cancer cells and how this changes patient response to anti-EGFR therapy.

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Dr Simpsonâ&#x20AC;&#x2122;s key finding was to develop a method to assay EGFR trafficking in human tumours using confocal microscopy with the discovery that EGFR internalisation is dysregulated in approximately 60% of patients. Current research projects: Receptor trafficking affects epithelial tumour treatment resistance The group has developed a method of imaging epidermal growth factor (EGF) internalisation over time in human tumors and methods of analysing EGFR. In analysing patient tumors we have found that in about 50% of patients, the EGFR fails to internalise in response to EGF binding. We are investigating this inhibition and its outcome for therapy resistance and to also determine whether we can correlate this dysregulation of EGFR trafficking with patient response to treatment. Receptor trafficking determines signal transduction output They are using dominant negative constructs that trap the EGFR at the plasma membrane to prevent its recycling from early endosomes back to the plasma membrane. Using a combination of EGF-stimulated and non-stimulated cells with SILAC mass-spectroscopy analysis, the team are investigating the spatio-temporal control of EGFR signalling. The HkRP family (Girdin, Daple and Gipie) are regulators of tumourigenesis and prognostic markers of metastasis Dr Simpson previously identified a family of proteins called the HkRP family. While originally described from a molecular and cellular analysis, these proteins have recently been shown to be involved in oncogensis and to have use as prognostic markers in cancers. The team continuing their molecular and cellular analysis of this protein family and investigating their behaviour in epithelial cancer.


Dr Ray Steptoe. Research Group: Miranda Coleman PhD Scholar, Jane Al-Kouba PhD scholar, Ritchie Hughes Masters Student, Robert Ling Honours Student, Tahra Camidge Research Assistant

Research provides the impetus underlying improved patient care. This is achieved through a combination of strong basic science and appropriate translational studies.

Dr Ray Steptoe More than 10% of Australians live with autoimmune and inflammatory diseases that result from dysregulated T-cell responses. Current treatments for autoimmune and inflammatory diseases provide only symptomatic relief. Immune therapies, however, have the potential to reverse destructive immune responses underlying these diseases and offer the prospect of a ‘cure’. Autoimmune and other T-cell mediated inflammatory diseases result when immune ‘tolerance’ mechanisms fail. In general, they are diagnosed only after onset of clinical symptoms when the immune system has already established an aberrant destructive response and tissue damage has occurred. Current treatments provide only symptomatic relief and no ‘curative’ therapies are available. As these diseases extract a profound personal, social and economic toll, there is an urgent need to develop effective curative therapies. Immune ‘tolerance’ normally prevents the immune system from mounting aberrant or pathogenic responses to normal body components. Therefore, a therapeutic that acts on the immune system (immunotherapy) to restore immune tolerance has the potential to ‘cure’ disease rather than merely alleviate symptoms and would fill this therapeutic need. Tissue destruction associated with autoimmune diseases is caused by effector and memory T cells. Therefore, to be successful, immunotherapy must purge, silence or regulate these cells in a way that is specific to the molecular triggers, or ‘antigens’; unique to each autoimmune disease. It was long believed that effector and memory T cell responses were resistant to tolerance induction. However, Dr Steptoe’s research has recently identified a method to ‘switch-off’ these unwanted T-cell responses. This opens up a new therapeutic approach which Dr Steptoe terms tolerogenic HPC therapy as a potential treatment of established autoimmune and T-cell mediated inflammatory disease. The overall goals of his research are to identify key mechanisms of tolerance, which cells,

with a particular focus on antigen-presenting cells, are important for ‘enforcing’ tolerance within the immune system and to understand how this knowledge can be exploited for the development of new immunotherapies. Current research projects: Cellular and molecular pathways of T-cell tolerance Autoimmunity and allergies develop when normal mechanisms restraining the immune system fail. Retraining the immune system through induction of T-cell tolerance is an attractive therapeutic. Molecular, biochemical and cellular approaches are used in their established models to define the pathways and interactions underlying induction and maintenance of T-cell tolerance. Prevention and reversal of autoimmune diabetes The group has previously shown that autoimmune (type 1) diabetes can be prevented by expression of key disease targets in dendritic cells. They are testing, in a range of models, proof-of-principle studies that establish whether diabetes-causing immune responses can be terminated. Reversing established allergies and allergic airways inflammation Allergies affect up to 20% of Australians and are a chief cause of asthma. The team are testing new ways to turn off allergic immune responses that we expect will limit allergen-induced allergic respiratory disease. Novel methods of gene delivery for tolerance Currently available methods limit the potential for clinical application of antigen-specific immunotherapeutic gene-therapy. Dr Steptoe’s team is seeking ways to develop vaccine-like approaches to facilitate gene-therapeutic induction of tolerance for application to autoimmune and inflammatory diseases.

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Dr Gethin Thomas. Research Group: Katelin Haynes Honours Student, Hsu-Wen Tseng PhD Student, Stuart Davidson PhD Student, Poh-Lynn Low Research Assistant

Bone diseases affect tens of millions of people worldwide and are often not detected until significant damage has occurred that is very difficult to repair. By developing new diagnostic tests and novel therapeutic approaches we can prevent the debilitating damage that often occurs in advanced skeletal disease.

Dr Gethin Thomas Ankylosing spondylitis is a debilitating form of arthritis affecting approximately 100,000 Australians for which there is no current cure. Ankylosing spondylitis is an arthritis specifically targeting the spine and pelvis. A hallmark of the disease is excessive bone formation which can result in complete joint fusion (ankylosis) leading to significant disability. No therapies are currently available that prevent or even slow this inevitable progression. The average age of onset is 26, leading to significant impacts on the workforce as well as the catastrophic effects on patients, with disease durations frequently over 20 years. Very little is known about how the disease progresses. Dr Thomas is currently investigating the changes occurring during this disease at the molecular, cellular and tissue level to identify new therapeutic approaches or to better target current options already available. Since completing his PhD, Dr Thomas has studied the biology of the skeleton; specifically the process of bone formation and the cells controlling that process; the osteoblasts. His interests focus on the roles of both novel and known genes in skeletal regulation and disease, in particular ankylosing spondylitis, and osteoporosis. His team utilises a combination of genome-wide association studies (GWAS), whole-genome expression profiling and large-scale mouse mutagenesis approaches to identify new genes involved in skeletal disease. His team then undertake functional analysis of these genes to understand their role in disease to aid the development of new diagnostic and therapeutic approaches. Previously, Dr Thomas led projects characterising novel bone genes which resulted in the identification and characterisation of two novel bone genes, Ostn and Bril, with Ostn being patented and targeted for drug development. More recently, he has focused on elucidation of the molecular mechanisms underlying the progression of ankylosing spondylitis to try to identify new targets for therapeutic development. Through a combination of genetic and transcriptomic profiling, his team is now testing new potential therapies in mouse models of

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ankylosing spondylitis. They have also demonstrated that key regulators of osteoblasts are dysregulated in mouse models of ankylosing spondylitis and they are also investigating ways of modulating their function to reduce the excessive bone formation, that is so debilitating in ankylosing spondylitis. Current research projects: Understanding the inflammation-bone formation interface The major long-term problem for patients with ankylosing spondylitis is the progressive stiffness of the spine that develops, occuring because the arthritis causes bone to form across affected joints, effectively fusing the joints, causing extreme disability. At this point, researchers do not know how this occurs, and they have no treatments that can stop it. The goal of these studies is to understand how the arthritis leads to new bone formation, and develop therapies for prevention. Dr Thomas’ group has established a number of mouse models of ankylosing spondylitis in our lab that closely mimic the human disease progression. Their studies to have identified several pathways that can be targeted to slow or even prevent disease progression, and they will be trialling therapies targeted at these pathways in their mouse models. Transcriptional and genetic profiling of ankylosing spondylitis The team’s previous studies have utilised gene expression profiling and genetic variation to identify novel genes associated with disease and generate gene lists that can predict early disease. To identify further candidate genes, they combine the genetic and gene expression data in an “eQTL” approach which is novel to ankylosing spondylitis. This will allow them to combine data from their genome-wide association studies with whole genome expression profiling, generating a unique powerful resource. The group are now embarking on further cutting-edge studies utilising next-generation sequencing to comprehensively define the ankylosing spondylitis transcriptome. Novel genes identified from these approaches can form the basis for new treatments and diagnostics.


Professor Ranjeny Thomas. Research Group: Annie An Research Assistant, Brendan O`Sullivan Senior Research Officer, Alexander Ghenassia Occupational Trainee, Dimeng Pang Student PhD, Srividya Katikireddi Clinical Research Fellow,Farshad Ghazanfari Clinical Research Fellow, Thiagarajan Sairam Visiting Qld-India Fellow, Emily Duggan Research Assistant, Helen Pahau Research Nurse and Student MPhil, Jared Velasco Research Assistant, Saion Chatterjee Summer Student, Karen Herd, Lab Manager and Research Assistant, Soi Law Honours Student, Merja Ruutu Research Officer, Helen Benham Student PhD, Ray Steptoe Senior Research Fellow, Roland Ruscher Student PhD, Katherine Irvine Research Officer, Hanno Nel Research Officer, Linda Rehaume Research Officer, Shayna Street Research Officer, Suman Yekollu Research Assistant

As a clinician, the suffering of patients with autoimmune disease drives me to apply my knowledge towards better treatments through research approaches, which will one day make it back to the clinic.

Professor Ranjeny Thomas Autoimmune diseases such as rheumatoid arthritis and childhood diabetes affect 8 in every 100 Australians, with pain, reduced work or school productivity and reduced lifespan. Autoimmune diseases such as type 1 diabetes and rheumatoid arthritis occur in people with a genetic background that puts them at risk, combined with specific environmental triggers that set off an inflammatory reaction. Professor Ranjeny Thomas’ research aims to understand essential inflammatory pathways in patients and animals with autoimmune disease that will identify markers of disease risk, and immune system targets for treatment. Professor Thomas’ research focuses on autoimmune diseases including rheumatoid arthritis. Her group completed trials of a proof-of-concept rheumatoid arthritis vaccine this year. Current research projects: Rheumatoid arthritis vaccine The team commenced a phase I clinical trial of a modified dendritic cell vaccine, known as Rheumavax. The vaccine consists of dendritic cells, grown in the laboratory from the blood of the patient to be immunised, and an antigen relevant to the disease. They administered Rheumavax to 18 patients with rheumatoid arthritis (RA) and found it to be well-tolerated with systemic effects on inflammation, immune regulation and glucose handling. To translate from this proof-ofconcept trial to a cell-free formulation, they generated nanoparticles containing a natural inhibitor, known as curcumin (from the spice turmeric), and antigen. They are taken up by dendritic cells in the lymph glands and represent a versatile platform technology, which can deliver different antigens or inhibitors. The curcumin nanoparticles also improved insulin sensitivity in obesity in mice, suggesting they may be of benefit for type 2 diabetes. They secured seed investment to develop the nanoparticle technology towards clinical trials in RA. Type 1 (childhood) diabetes In mice, they are testing the capacity of their nanoparticles to block inflammation and disease, which could be translated into human trials. In children with recent-onset type 1 diabetes who were controlled

with insulin shots, blood cells known as monocytes showed strong expression of genes of cellular stress. The more that cellular stress genes were activated, the more insulin was required to control blood glucose and the less likely patients were to settle into a period of remission or “honeymoon” after diagnosis. This test may predict a bad prognosis after diagnosis of diabetes in children. Ankylosing spondylitis, psoriatic arthritis and Crohn’s disease This group of diseases is known as the spondyloarthropathies. A number of genes are known to be associated with these diseases, which are thought to be triggered by infection or interaction of the predisposed immune system with bacteria normally residing in the gut, on the skin or in the genital tract. The team found that a mouse model, known as SKG, which has a mutation reducing immune signalling in T lymphocytes, develops spondyloarthropathy when injected with beta-glucan, a component of fungal and bacterial cell walls. The arthritis is dependent on T lymphocytes and an inflammatory mediator called interleukin-23. The interleukin-23 and CARD-9, a gene which transduces signals from beta-glucan in cells are key genes associated with human ankylosing spondylitis, psoriatic arthritis and Crohn’s disease. This exciting finding will help to rapidly piece together how microbes and genes come together to alter the immune system in human spondyloarthropathies, so Professor Thomas and her team can design better treatments. Using dendritic cells to suppress autoimmune disease Mice deficient in the gene RelB have severe spontaneous autoimmune inflammatory disease of the liver, pancreas and eyes. They also develop asthma and dermatitis. The group found that a single treatment with RelB-expressing dendritic cells was able to cure these mice of their disease. The clinical improvement depended on efficient stimulation of T lymphocytes by the transferred dendritic cells, causing interferon-gamma to be produced and to regulate inflammation through an enzyme called IDO. This model has important implications for the treatment of asthma and autoimmune diseases, particularly where interferon-gamma production or responsiveness is deficient.

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Professor Peter Visscher. Research Group: Jian Yang Research Fellow, Allan McRae Research Fellow, Joseph Powell Research Officer, Gib Hemani Postdoctoral Statistical Geneticist, Anita Goldinger Research Assistant

What inspires me is the curiosity to better understand individual differences between people in complex traits, including susceptibility to disease, and to use elegant computational and statistical tools with appropriate data to achieve that goal.

Professor Peter Visscher Current research projects: Understanding genetic variation for complex traits in human populations The Visscher lab specialises in quantitative and statistical genetics, population genetics, human genetics and bioinformatics, with the ultimate aim of trying to understand the genetic basis of differences in risk to disease and other phenotypes such as cognitive ability, between individuals. Professor Visscherâ&#x20AC;&#x2122;s research uses theoretical derivations, simulation studies, development of new analytical methods and software tools and the application of advanced statistical analysis methods to genetic and phenotypic data. In 2011 the group continued to demonstrate, using innovative statistical methods, that complex traits in human populations, including common diseases and traits such as height, body-mass-index and cognitive ability, are caused by the cumulative effect of hundreds of genes. They have contributed analysis expertise to a large number of international research consortia that have found genes affecting endometriosis, schizophrenia, asthma, circulating lipid levels,

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rheumatoid arthritis and stature. The Visscher lab continues to lead the analysis efforts of a number of international research consortia. They have developed widely-used statistical methods and software to estimate the effects of genes, chromosomes and the whole genome on disease susceptibility. Using data from 3,500 individuals from Scotland and England, for whom the group had measures of DNA variation on 500,000 genetic markers and outcomes of psychometric tests, the group showed that adult intelligence is highly heritable and caused by the cumulative of hundreds if not thousands of genes. This work is the continuation of a long-standing collaboration with Professor Ian Deary from the University of Edinburgh. Professor Deary is the Director of the Centre for Cognitive Ageing and Cognitive Epidemiology at the University of Edinburgh, of which Professor Visscher is a member. In collaboration with researchers from the Queensland Institute of Medical Research (QIMR), Professor Visscher has established the Brisbane Systems Genetics Study, with the aim to understand genetic variation in gene expression and its correlation with individual differences in complex traits.


Dr James Wells. Research Group: Jennifer Bridge Research Assistant, Sally Wu Summer Student

Vaccines have proven time and again that they have an immense capacity to protect us from disease. I believe we can also harness vaccines to cure existing diseases, and through my work, I hope to provide new cures for cancer.

Dr James Wells Australia has the highest rate of non-melanoma skin cancer in the world - there are over 300,000 new cases each year. Traditionally, vaccines prevent us from getting sick from infections that we have not yet been exposed to. However, new vaccines are being developed to treat problems we already have, such as cancer. In order to develop these vaccines we must first understand how cancer and the immune system influence one another. Dr Wells studies how to develop therapeutic vaccines for cancer treatment. Therapeutic vaccines differ from conventional vaccines in that rather than priming the immune system to prevent the establishment of an infection, they must redirect existing immune responses to allow for cancer cell recognition and their subsequent destruction. Dr Wellsâ&#x20AC;&#x2122; research program aims to develop a therapeutic cancer vaccine for a common skin cancer known as Squamous Cell Carcinoma, or SCC.

SCC is a significant health problem in Australia, particularly in Northern New South Wales and Queensland, due to the high levels of ultraviolet radiation from the sun. A newly established group, Dr Wells will focus on determining how skin cancer induced by ultraviolet light prevents anti-cancer immune responses from destroying cancer lesions in the skin. In doing so, he hopes to uncover new technologies for the rapid development of therapeutic vaccines to treat a wide range of cancers. Current research projects: 1. Characterising the immunopathology of Squamous Cell Carcinoma of the skin 2. The development of novel therapeutic vaccines for the treatment of established skin cancer 3. Breaking skin cancer-associated immune tolerance

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Publications Brown Bradbury LA, Barlow S, Geoghegan F, Hannon RA, Stuckey SL, Wass JA, Russell RG, Brown MA, Duncan EL. Risedronate in adults with osteogenesis imperfecta type I: increased bone mineral density and decreased bone turnover, but high fracture rate persists. Osteoporos Int. 2011 Jul 8. [Epub ahead of print] “Brown MA. Progress in the genetics of ankylosing spondylitis. Brief Funct Genomics. 2011 Sep;10(5):249-57. doi: 10.1093/bfgp/ elr023. Epub 2011 Sep 30. PubMed PMID: 21965815.” “Burdon KP, Macgregor S, Hewitt AW, Sharma S, Chidlow G, Mills RA, Danoy P, Casson R, Viswanathan AC, Liu JZ, Landers J, Henders AK, Wood J, Souzeau E, Crawford A, Leo P, Wang JJ, Rochtchina E, Nyholt DR, Martin NG, Montgomery GW, Mitchell P, Brown MA, Mackey DA, Craig JE. Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1. Nature Genetics 2011 Jun;43(6):574-8. Epub 2011 May 1”

“Duncan EL, Danoy P, Kemp JP, Leo PJ, McCloskey E, Nicholson GC, Eastell R, Prince RL, Eisman JA, Jones G, Sambrook PN, Reid IR, Dennison EM, Wark J, Richards JB, Uitterlinden AG, Spector TD, Esapa C, Cox RD, Brown SD, Thakker RV, Addison KA, Bradbury LA, Center JR, Cooper C, Cremin C, Estrada K, Felsenberg D, Glüer CC, Hadler J, Henry MJ, Hofman A, Kotowicz MA, Makovey J, Nguyen SC, Nguyen TV, Pasco JA, Pryce K, Reid DM, Rivadeneira F, Roux C, Stefansson K, Styrkarsdottir U, Thorleifsson G, Tichawangana R, Evans DM, Brown MA. Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk. PLoS Genet. 2011 Apr;7(4):e1001372. Epub 2011 Apr 21.”

Couto AR, Zhang Y, Timms A, Bruges-Armas J, Sequeiros J, Brown MA. Investigating ANKH and ENPP1 in Slovakian families with chondrocalcinosis. Rheumatol Int. 2011 Aug 3. [Epub ahead of print] PubMed PMID: 21811784.

“Ferreira MA, Matheson MC, Duffy DL, Marks GB, Hui J, Le Souaf P, Danoy P, Baltic S, Nyholt DR, Jenkins M, Hayden C, Willemsen G, Ang W, Kuokkanen M, Beilby J, Cheah F, de Geus EJ, Ramasamy A, Vedantam S, Salomaa V, Madden PA, Heath AC, Hopper JL, Visscher PM, Musk B, Leeder SR, Jarvelin MR, Pennell C, Boomsma DI, Hirschhorn JN, Walters H, Martin NG, James A, Jones G, Abramson MJ, Robertson CF, Dharmage SC, Brown MA, Montgomery GW, Thompson PJ; Australian Asthma Genetics Consortium. Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. Lancet. 2011 Sep 10;378(9795): 1006-14. PubMed PMID: 21907864”

Danoy P, Wei M, Johanna H, Jiang L, He D, Sun L, Zeng X, Visscher PM, Brown MA, Xu H. Association of variants in MMEL1 and CTLA4 with rheumatoid arthritis in the Han Chinese population. Ann Rheum Dis. 2011 Oct; 70(10):1793-7. Epub 2011 Jul 21. PubMed PMID: 21784728.

“Fischer R, Trudgian DC, Wright C, Thomas G, Bradbury LA, Brown MA, Bowness P, Kessler BM. Discovery of candidate serum proteomic and metabolomic biomarkers in Ankylosing Spondylitis. Mol Cell Proteomics. 2011 Oct 13. [Epub ahead of print] PubMed PMID: 21997733.”

Davidson S, Jiang L, Glazov E, Cortes A, Donskoi M, Danoy P, Thomas G, Xu H, Brown M. The application of next-generation sequencing to identify novel ankylosing spondylitis-associated IL23R variants in a han chinese population. Internal Medicine Journal 41(Suppl 1):22-22 MAY 2011

Glazov EA, Zankl A, Donskoi M, Kenna TJ, Thomas GP, Clark GR, Duncan EL, Brown MA. Whole-exome re-sequencing in a family quartet identifies POP1 mutations as the cause of a novel skeletal dysplasia. PLoS Genet. 2011 Mar;7(3):e1002027. Epub 2011 Mar 24.

Cortes A, Danoy P, Wordsworth B, Stone M, Morgan A, Marzo-Ortega H, Ward M, Corr M, Reveille J, Weisman M, Brown M. MMP1 polymorphisms are associated with severity of radiographic measures of ankylosing spondylitis. Source: INTERNAL MEDICINE JOURNAL 41(Suppl 1): 22-22 MAY 2011

K. Estradaa, E. Evangeloub, Y.-H. Hsu, U. Styrkarsdottird, C.-T. Liue, A. Moayyerif, S. Kaptogef, E. Duncang, N. Amina, D. Kielc, D. Karasikc, O.M. Albaghah, M. Browng, T.D. Spectori, M.C. Zillikensa, C. Ohlssonj, G. Thorleifssond, J. Reevef, L. Vandenputj, U. Petterssonk, T. O’Neilll, J.A. Rianchom, O. ljunggrenn, F. Rousseauo, W.D. Lesliep, B. Obermayer-Pietschq, N. Alonsoh, B. Langdahlr, X. Noguéss, R. Princet, P. Lipsu, S. Chengv, J. Marcw, P. Kolliax, M.L. Brandiy, L. Hockingz, E. Khusnutdinaaa, C. Cooperab, T. Lehtimäkiac, R. Jacksonad, J.-M. Kohae, R.L. Minsteraf, L. Yerges-Armstrongag, B. Richardsah, N. Glazerai, A. Kungaj, D. Kollerak, D. Evansal, J. Ioannidisb, S.H. Ralstonh, A.G. Uitterlindena, F. Rivadeneiraa

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and for the AOGC, GEFOS and GENOMOS consortia. Association analyses of 47,500 individuals identifies six fracture loci and 82 BMD loci clustering in biological pathways that regulate osteoblast and osteoclast activity. Bone 2011 May;48(Suppl 2):S69-S69

“International Multiple Sclerosis Genetics Consortium; Wellcome Trust Case Control Consortium 2, Sawcer S, Hellenthal G, Pirinen M, Spencer CC, Patsopoulos NA, Moutsianas L, Dilthey A, Su Z, Freeman C, Hunt SE, Edkins S, Gray E, Booth DR, Potter SC, Goris A, Band G, Oturai AB, Strange A, Saarela J, Bellenguez C, Fontaine B, Gillman M, Hemmer B, Gwilliam R, Zipp F, Jayakumar A, Martin R, Leslie S, Hawkins S, Giannoulatou E, D’alfonso S, Blackburn H, Boneschi FM, Liddle J, Harbo HF, Perez ML, Spurkland A, Waller MJ, Mycko MP, Ricketts M, Comabella M, Hammond N, Kockum I, McCann OT, Ban M, Whittaker P, Kemppinen A, Weston P, Hawkins C, Widaa S, Zajicek J, Dronov S, Robertson N, Bumpstead SJ, Barcellos LF, Ravindrarajah R, Abraham R, Alfredsson L, Ardlie K, Aubin C, Baker A, Baker

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Knouff CW, Thompson JR, Horne BD, Stewart AF, Assimes TL, Wild PS, Allayee H, Nitschke PL, Patel RS; Myocardial Infarction Genetics Consortium; Wellcome Trust Case Control Consortium, Martinelli N, Girelli D, Quyyumi AA, Anderson JL, Erdmann J, Hall AS, Schunkert H, Quertermous T, Blankenberg S, Hazen SL, Roberts R, Kathiresan S, Samani NJ, Epstein SE, Rader DJ. Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies. Lancet. 2011 Jan 29;377(9763):383-92. Epub 2011 Jan 14. “Ripke S, Sanders AR, Kendler KS, Levinson DF, Sklar P, Holmans PA, Lin DY, Duan J, Ophoff RA, Andreassen OA, Scolnick E, Cichon S, St Clair D, Corvin A, Gurling H, Werge T, Rujescu D, Blackwood DH, Pato CN, Malhotra AK, Purcell S, Dudbridge F, Neale BM, Rossin L, Visscher PM, Posthuma D, Ruderfer DM, Fanous A, Stefansson H, Steinberg S, Mowry BJ, Golimbet V, De Hert M, Jansson EG, Bitter I, Pietilainen OP, Collier DA, Tosato S, Agartz I, Albus M, Alexander M, Amdur RL, Amin F, Bass N, Bergen SE, Black DW, Barglum AD, Brown MA, Bruggeman R, Buccola NG, Byerley WF, Cahn W, Cantor RM, Carr VJ, Catts SV, Choudhury K, Cloninger CR, Cormican P, Craddock N, Danoy PA, Datta S, de Haan L, Demontis D, Dikeos D, Djurovic S, Donnelly P, Donohoe G, Duong L, Dwyer S, Fink-Jensen A, Freedman R, Freimer NB, Friedl M, Georgieva L, Giegling I, Gill M, Glenthaj B, Godard S, Hamshere M, Hansen M, Hansen T, Hartmann AM, Henskens FA, Hougaard DM, Hultman CM, Ingason A, Jablensky AV, Jakobsen KD, Jay M, Jürgens G, Kahn RS, Keller MC, Kenis G, Kenny E, Kim Y, Kirov GK, Konnerth H, Konte B, Krabbendam L, Krasucki R, Lasseter VK, Laurent C, Lawrence J, Lencz T, Lerer FB, Liang KY, Lichtenstein P, Lieberman JA, Linszen DH, Lannqvist J, Loughland CM, Maclean AW, Maher BS, Maier W, Mallet J, Malloy P, Mattheisen M, Mattingsdal M, McGhee KA, McGrath JJ, McIntosh A, McLean DE, McQuillin A, Melle I, Michie PT, Milanova V, Morris DW, Mors O, Mortensen PB, Moskvina V, Muglia P, Myin-Germeys I, Nertney DA, Nestadt G, Nielsen J, Nikolov I, Nordentoft M, Norton N, Nathen MM, O’Dushlaine CT, Olincy A, Olsen L, O’Neill FA, Orntoft TF, Owen MJ, Pantelis C, Papadimitriou G, Pato MT, Peltonen L, Petursson H, Pickard B, Pimm J, Pulver AE, Puri V, Quested D, Quinn EM, Rasmussen HB, Rathelyi JM, Ribble R, Rietschel M, Riley BP, Ruggeri M, Schall U, Schulze TG, Schwab SG, Scott RJ, Shi J, Sigurdsson E, Silverman JM, pencer CC, Stefansson K, Strange A, Strengman E, Stroup TS, Suvisaari J, Terenius L, Thirumalai S, Thygesen JH, Timm S, Toncheva D, van den Oord E, van Os J, van Winkel R, Veldink J, Walsh D, Wang AG, Wiersma D, Wildenauer DB, Williams HJ, Williams NM, Wormley B, Zammit S, Sullivan PF, O’Donovan MC, Daly MJ, Gejman PV; Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium. Genome-wide association study

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Publications cont. identifies five new schizophrenia loci. Nat Genet. 2011 Sep 18;43(10):969-76. doi: 10.1038/ng.940. PubMed PMID: 21926974.” Ritchie ME, Liu R, Carvalho BS; Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene), Irizarry RA. Comparing genotyping algorithms for Illumina’s Infinium whole-genome SNP BeadChips. BMC Bioinformatics. 2011 Mar 8;12:68. PubMed PMID: 21385424; PubMed Central PMCID: PMC3063825. “Sobrin L, Green T, Sim X, Jensen RA, Tai ES, Tay WT, Wang JJ, Mitchell P, Sandholm N, Liu Y, Hietala K, Iyengar SK; Family Investigation of Nephropathy and Diabetes-Eye Research Group, Brooks M, Buraczynska M, Van Zuydam N, Smith AV, Gudnason V, Doney AS, Morris AD, Leese GP, Palmer CN; Wellcome Trust Case Control Consortium 2, Swaroop A, Taylor HA Jr, Wilson JG, Penman A, Chen CJ, Groop PH, Saw SM, Aung T, Klein BE, Rotter JI, Siscovick DS, Cotch MF, Klein R, Daly MJ, Wong TY. Candidate gene association study for diabetic retinopathy in persons with type 2 diabetes: the Candidate gene Association Resource (CARe). Invest Ophthalmol Vis Sci. 2011 Sep 29;52(10):7593-602. Print 2011 Sep. PubMed PMID: 21873659; PubMed Central PMCID: PMC3183981.” The Australo-Anglo-American Spondyloarthritis Consortium (TASC), the Wellcome Trust Case Control Consortium 2 (WTCCC2), David M Evans, Chris C A Spencer, Jennifer J Pointon, Zhan Su, David Harvey, Grazyna Kochan, Udo Oppermann, Alexander Dilthey, Matti Pirinen, Millicent A Stone, Louise Appleton, Loukas Moutsianas, Stephen Leslie, Tom Wordsworth, Tony J Kenna, Tugce Karaderi, Gethin P Thomas, Michael M Ward, Michael H Weisman, Claire Farrar, Linda A Bradbury, Patrick Danoy, Robert D Inman, Walter Maksymowych, Dafna Gladman, Proton Rahman, Spondyloarthritis Research Consortium of Canada (SPARCC), Ann Morgan, Helena Marzo-Ortega, Paul Bowness, Karl Gaffney, J S Hill Gaston, Malcolm Smith, Jacome Bruges-Armas, Ana-Rita Couto, Rosa Sorrentino, Fabiana Paladini, Manuel A Ferreira, Huji Xu, Yu Liu, Lei Jiang, Carlos Lopez-Larrea, Roberto Díaz-Peña, Antonio López-Vázquez, Tetyana Zayats, Gavin Band, Céline Bellenguez, Hannah Blackburn, Jenefer M Blackwell, Elvira Bramon, Suzannah J Bumpstead, Juan P Casas, Aiden Corvin, Nicholas Craddock, Panos Deloukas, Serge Dronov, Audrey Duncanson, Sarah Edkins, Colin Freeman, Matthew Gillman, Emma Gray, Rhian Gwilliam, Naomi Hammond, Sarah E Hunt, Janusz Jankowski, Alagurevathi Jayakumar, Cordelia Langford, Jennifer Liddle, Hugh S Markus, Christopher G Mathew, Owen T McCann, Mark I McCarthy, Colin N A Palmer, Leena Peltonen, Robert Plomin, Simon C Potter, Anna Rautanen, Radhi Ravindrarajah, Michelle Ricketts, Nilesh Samani, Stephen J Sawcer, Amy Strange, Richard C Trembath, Ananth C Viswanathan, Matthew Waller, Paul Weston, Pamela Whittaker, Sara Widaa, Nicholas W Wood, Gilean McVean, John D Reveille, B Paul Wordsworth, Matthew A Brown & Peter Donnelly. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-

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B27 in disease susceptibility. Nature Genetics VOLUME 43 NUMBER 8 AUGUST 2011 Thomas G, Duan R, Pettit A , Glant T, Brown M. Altered WNT-signalling links inflammation and bony ankylosis in a mouse model of ankylosing spondylitis. Internal Medicine Journal 41(Suppl 1): 3-3 MAY 2011Cortes A, Brown MA. Promise and pitfalls of the Immunochip. Arthritis Res Ther 2011 Feb 1;13(1):101. [Epub ahead of print]

Frazer “Bhat P, Mattarollo SR, Gosmann C, Frazer IH, Leggatt GR. Regulation of immune responses to HPV infection and during HPV-directed immunotherapy. Immunol Rev. 2011 Jan;239(1):85-98. doi: 10.1111/j.1600065X.2010.00966.x. Review. PubMed PMID: 21198666.” Chen X, Fernando GJ, Crichton ML, Flaim C, Yukiko SR, Fairmaid EJ, Corbett HJ, Primiero CA, Ansaldo AB, Frazer IH, Brown LE, Kendall MA. Improving the reach of vaccines to lowresource regions, with a needle-free vaccine delivery device and long-term thermostabilization. J Control Release. 2011 Jun 30;152(3):349-55. doi: 10.1016/j.jconrel.2011.02.026. Epub 2011 Mar 1. PubMed PMID: 21371510. Frazer IH, Leggatt GR, Mattarollo SR. Prevention and treatment of papillomavirus-related cancers through immunization. Annu Rev Immunol. 2011 Apr 23;29:111-38. Review. “Frazer IH, Levin MJ. Paradigm shifting vaccines: prophylactic vaccines against latent varicella-zoster virus infection and against HPV-associated cancer. Curr Opin Virol. 2011 Oct 1;1(4):268-279. PubMed PMID: 21984890; PubMed Central PMCID: PMC3185382.” “Mattarollo SR, Yong M, Gosmann C, Choyce A, Chan D, Leggatt GR, Frazer IH. NKT cells inhibit antigen-specific effector CD8 T cell induction to skin viral proteins. J Immunol. 2011 Aug 15;187(4):1601-8. Epub 2011 Jul 8. PubMed PMID: 21742969; PubMed Central PMCID: PMC3150369” “Maugeri N, Powell JE, ‘t Hoen PA, de Geus EJ, Willemsen G, Kattenberg M, Henders AK, Wallace L, Penninx B, Hottenga JJ, Medland SE, Saviouk V, Martin NG, Visscher PM, van Ommen GJ, Frazer IH, Boomsma DI, Montgomery GW, Ferreira MA. LPAR1 and ITGA4 regulate peripheral blood monocyte counts. Hum Mutat. 2011 Aug;32(8):873-6. doi: 10.1002/humu.21536. Epub 2011 Jul 12. PubMed PMID: 21598361.” “Ruutu MP, Chen X, Joshi O, Kendall MA, Frazer IH. Increasing mechanical stimulus induces migration of Langerhans cells and impairs the immune response to intracutaneously delivered antigen. Exp Dermatol. 2011 Jun;20(6):534-6. doi: 10.1111/j.1600-0625.2010.01234.x. Epub 2011 Apr 4. PubMed PMID: 21457356.” Zhou F, Leggatt GR, Frazer IH. Human papillomavirus 16 E7 protein inhibits interferongamma-mediated enhancement of keratinocyte antigen processing and T-cell lysis. FEBS JOURNAL. 2011 Apr;278(6):955-63. doi: 10.1111/j.17424658.2011.08011.x. Epub 2011 Feb 5.

Frazer/Bhat Bhat P, Snooks MJ, Anderson DA. Hepatocytes traffic and export hepatitis B virus basolaterally by polarity-dependent mechanisms. J Virol. 2011 Dec;85(23):12474-81. Epub 2011 Sep 21. PubMed PMID: 21937643; PubMed Central PMCID: PMC3209395. Gabrielli Astuti P, Gabrielli B. Phosphorylation of Cdc25B3 Ser169 regulates 14-3-3 binding to Ser151 and Cdc25B activity. Cell Cycle. 2011 Jun 15;10(12):1960-7. Epub 2011 Jun 15. PubMed PMID: 21558810 Boutros R, Lorenzo C, Mondesert O, Jauneau A, Oakes V, Dozier C, Gabrielli B, Ducommun B. CDC25B associates with a centrin 2-containing complex and is involved in maintaining centrosome integrity. Biol Cell. 2011 Feb;103(2):55-68. Gabrielli B, Chia K, Warrener R. Finally, how histone deacetylase inhibitors disrupt mitosis! Cell Cycle. 2011 Aug 15;10(16):2658-61. Epub 2011 Aug 15. PubMed PMID: 21811095. Deleyrolle LP, Harding A, Cato K, Siebzehnrubl FA, Rahman M, Azari H, Olson S, Gabrielli B, Osborne G, Vescovi A, Reynolds BA. Evidence for label-retaining tumour-initiating cells in human glioblastoma. Brain. 2011 May;134 (Pt 5):1331-43. Epub 2011 Apr 22. PubMed PMID: 21515906; PubMed Central PMCID: PMC3097894

Gabrielli-Leggatt Leggatt GR, Gabrielli B. Histone deacetylase inhibitors in the generation of the anti-tumour immune response. Immunol Cell Biol. 2011 Nov 8. doi: 10.1038/icb.2011.94. [Epub ahead of print] PubMed PMID: 22064708.

Gonda Dredge K, Hammond E, Handley P, Gonda TJ, Smith MT, Vincent C, Brandt R, Ferro V, Bytheway I. PG545, a dual heparanase and angiogenesis inhibitor, induces potent anti-tumour and anti-metastatic efficacy in preclinical models. Br J Cancer 2011 Feb 15;104(4):635-42. Epub 2011 Feb 1. Hugo HJ, Drabsch Y, Gonda TJ, Blick T, Ramsay RG, Thompson EW. Epithelial-mesenchymal plasticity dictates proliferative control pathways in breast cancer. Clinical & Experimental Metastasis 2011 Feb;28(2):173-174 Ranall MV, Gabrielli BG, Gonda TJ. High-content imaging of neutral lipid droplets with 1,6-diphenylhexatriene. Biotechniques. 2011 Jul;51(1):35-6, 38-42. PubMed PMID: 21781051. Skalamera D, Ranall MV, Wilson BM, Leo P, Purdon AS, Hyde C, Nourbakhsh E, Grimmond SM, Barry SC, Gabrielli B, Gonda TJ. A HighThroughput Platform for Lentiviral Overexpression Screening of the Human ORFeome. PLoS One. 2011;6(5):e20057. Epub 2011 May 24.

Gonda/ Brown Zhao L, Glazov EA, Pattabiraman DR, Al-Owaidi F, Zhang P, Brown MA, Leo PJ, Gonda TJ. Integrated genome-wide chromatin occupancy and expression analyses identify key myeloid pro-differentiation transcription factors repressed by Myb. Nucleic Acids Res. 2011 Jun 1;39(11):4664-79. Epub 2011 Feb 11.


Harding Deleyrolle LP, Harding A, Cato K, Siebzehnrubl FA, Rahman M, Azari H, Olson S, Gabrielli B, Osborne G, Vescovi A, Reynolds BA. Evidence for label-retaining tumour-initiating cells in human glioblastoma. Brain. 2011 May;134 (Pt 5):1331-43. Epub 2011 Apr 22.

Hickman Chachay VS, Kirkpatrick CM, Hickman IJ, Ferguson M, Prins JB, Martin JH. Resveratrol pills to replace a healthy diet? Br J Clin Pharmacol. 2011 Jul;72(1):27-38. Epub June 9 Orazio LK, Isbel NM, Armstrong KA, Tarnarskyj J, Johnson DW, Hale RE, Kaisar M, Banks MD, Hickman IJ. Evaluation of Dietetic Advice for Modification of Cardiovascular Disease Risk Factors in Renal Transplant Recipients. J Ren Nutr. 2011 Mar 29. [Epub ahead of print] Rossi M , Hickman IJ. Diet prescription for non-alcoholic fatty liver disease: Is it worth the effort? A systematic review. Nutrition & Dietetics MAR 2011;68(1):33-40

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“Singhania A, Wu SY, McMillan NA. Effective Delivery of PEGylated siRNA-Containing Lipoplexes to Extraperitoneal Tumours following Intraperitoneal Administration. J Drug Deliv. 2011;2011:192562. Epub 2011 Jun 7. PubMed PMID: 21773042; PubMed Central PMCID: PMC3134833.” Truong NP, Jia Z, Burgess M, McMillan NA, Monteiro MJ. Self-Catalyzed Degradation of Linear Cationic Poly(2-Dimethylaminoethyl Acrylate) in Water. Biomacromolecules.2011 May 9;12(5):1876-82. Epub 2011 Apr 25. Wu SY, Chang HI, Burgess M, McMillan NA. Vaginal delivery of siRNA using a novel PEGylated lipoplex-entrapped alginate scaffold system. J Control Release. 2011 Feb 17. [Epub ahead of print] Truong NP, Jia Z, Burgess M, Payne L, McMillan NA, Monteiro MJ. Self-catalyzed degradable cationic polymer for release of DNA. Biomacromolecules. 2011 Oct 10;12(10):3540-8. Epub 2011 Aug 31. PubMed PMID: 21838265

McMillan /Saunders

Cho KJ, Hill MM, Chigurupati S, Du G, Parton RG, Hancock JF. Therapeutic levels of the hydroxmethylglutaryl-coenzyme A reductase inhibitor lovastatin activate ras signaling via phospholipase D2. Mol Cell Biol 2011 Mar;31(6):1110-20. Epub 2011 Jan 18

“Antonsson A, Spurr TP, Chen AC, Francis GD, McMillan NA, Saunders NA, Law M, Bennett IC. High prevalence of human papillomaviruses in fresh frozen breast cancer samples. J Med Virol. 2011 Dec;83(12):2157-63. doi: 10.1002/ jmv.22223. PubMed PMID: 22012724.”

Davies JM, Voskamp A, Dang TD, Pettit B, Loo D, Petersen A, Hill MM, Upham JW, Rolland JM, O’Hehir RE. The dominant 55 kDa allergen of the subtropical Bahia grass (Paspalum notatum) pollen is a group 13 pollen allergen, Pas n 13. Mol Immunol 2011 Mar;48(6-7): 931-40. Epub 2011 Jan 26..

“Lane S, Gill D, McMillan NA, Saunders N, Murphy R, Spurr T, Keane C, Fan HM, Mollee P. Valproic acid combined with cytosine arabinoside in elderly patients with acute myeloid leukemia has in vitro but limited clinical activity. Leuk Lymphoma. 2011 Nov 21. [Epub ahead of print] PubMed PMID: 22098405.”

“Inder KL, Zheng YZ, Davis MJ, Moon H, Loo D, Nguyen H, Clements JA, Parton RG, Foster LJ, Hill MM. Expression of PTRF in PC-3 cells modulates cholesterol dynamics and the actin cytoskeleton impacting secretion pathways. Mol Cell Proteomics. 2011 Oct 26. [Epub ahead of print] PubMed PMID: 22030351”

Chia KM, Liu J, Francis GD, Naderi A. A feedback loop between androgen receptor and ERK signaling in estrogen receptor-negative breast cancer. Neoplasia 2011 Feb;13(2):154-66

Zheng YZ, Boscher C, Inder KL, Fairbank M, Loo D, Hill MM, Nabi IR, Foster LJ. Differential impact of caveolae and caveolin-1 scaffolds on the membrane raft proteome. Mol Cell Proteomics. 2011 Oct;10(10):M110.007146. Epub 2011 Jul 13. PubMed PMID: 21753190; PubMed Central PMCID: PMC3205860.

McMillan Chen AC, Waterboer T, Keleher A, Morrison B, Jindal S, McMillan D, Nicol D, Gardiner RA, McMillan NA, Antonsson A. Human Papillomavirus in Benign Prostatic Hyperplasia and Prostatic Adenocarcinoma Patients. Pathol Oncol Res. 2011 Jan 16. [Epub ahead of print] Khairuddin N, Gantier MP, Blake SJ, Wu SY, Behlke MA, Williams BR, McMillan NA. siRNA-induced immunostimulation through TLR7 promotes antitumoral activity against HPV-driven tumors in vivo. Immunol Cell Biol. 2011 Mar 22. [Epub ahead of print]

Naderi

Naderi A, Chia KM, Liu J. Synergy between inhibitors of androgen receptor and MEK has therapeutic implications in estrogen receptornegative breast cancer. Breast Cancer Res 2011 Apr 1;13(2):R36. [Epub ahead of print] Naderi A, Liu J, Francis GD. A feedback loop between BEX2 and ErbB2 mediated by c-Jun signaling in breast cancer. Int J Cancer. 2011 Feb 3. doi: 10.1002/ijc.25977. [Epub ahead of print]

Saunders “Bissett SL, Howell-Jones R, Swift C, De Silva N, Biscornet L, Parry JV, Saunders NA, Nathan M, Soldan K, Szarewski A, Cuzick J, Beddows S. Human papillomavirus genotype detection and viral load in paired genital and urine samples from both females and males. J Med Virol. 2011 Oct;83(10):1744-51. doi: 10.1002/ jmv.22167. PubMed PMID: 21837790.” “Gan CP, Hamid S, Hor SY, Zain RB, Ismail SM, Wan Mustafa WM, Teo SH, Saunders N, Cheong SC. Valproic acid: Growth inhibition of head and neck cancer by induction of terminal differentiation and senescence. Head Neck. 2011 Mar 24. doi: 10.1002/hed.21734. [Epub ahead of print]”

Hazar-Rethinam M, Cameron SR, Dahler AL, Endo-Munoz LB, Smith L, Rickwood D, Saunders NA. Loss of E2F7 Expression Is an Early Event in Squamous Differentiation and Causes Derepression of the Key Differentiation Activator Sp1. J Invest Dermatol 2011 May;131(5):1077-84. Epub 2011 Jan 20.

Steptoe Shah N, Steptoe RJ, Parekh HS. Low-generation asymmetric dendrimers exhibit minimal toxicity and effectively complex DNA. J Pept Sci. 2011 Jun;17(6):470-8. doi: 10.1002/psc.1347. Epub 2011 Feb 24.

T homas “McNally A, Hill GR, Sparwasser T, Thomas R, Steptoe RJ. CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7529-34. Epub 2011 Apr18. PubMed PMID: 21502514; PubMed Central PMCID: PMC3088596.” “O’Sullivan BJ, Pai S, Street S, An X, MacDonald KP, Wong M, Strutton G, Gerondakis S, Steptoe RJ, de St Groth BF, Hill GR, Thomas R. Immunotherapy with costimulatory dendritic cells to control autoimmune inflammation. J Immunol. 2011 Oct 15;187(8):4018-30. Epub 2011 Sep 7. PubMed PMID: 21900177.” “Shklovskaya E, O’Sullivan BJ, Ng LG, Roediger B, Thomas R, Weninger W, Fazekas de St Groth B. Langerhans cells are precommitted to immune tolerance induction. Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):18049-18054. Epub 2011 Oct 17. PubMed PMID: 22006331; PubMed Central PMCID: PMC3207689” Street S, Purcell A, Law S, Yu A, Capini C, O’Sullivan B, Pahau H, Thomas R. Proinflammatory and regulatory t cell responses to citrullinated autoantigenic peptides in peripheral blood of shared epitope plus rheumatoid arthritis patients.Internal Medicine Journal 41(Suppl 1):14-14 MAY 2011 White D, Pahau H, Duggan E, Paul S, Thomas R. Outcome of an intensive treat-to-target disease modifying drug regimen in early rheumatoid arthritis within the first month sets the response trajectory for one year. Internal Medicine Journal. 41 (Suppl 1):42-42 MAY 2011 Yekollu SK, Thomas R, O’Sullivan B. Targeting Curcusomes to Inflammatory Dendritic Cells Inhibits NF-{kappa}B and Improves Insulin Resistance in Obese Mice. Diabetes. 2011 Nov;60(11):2928-38. Epub 2011 Sep 1. PubMed PMID: 21885868; PubMed Central PMCID: PMC3198103.

Thomas/Steptoe McNally A, Hill GR, Sparwasser T, Thomas R, Steptoe RJ. CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7529-34. Epub 2011 Apr 18.

51


Collaborations Professor Matt Brown 1. Professor Paul Wordsworth, University of Oxford, UK. 2. Professor John Reveille, University of Texas (Houston), USA. 3. Professor Huji Xu, Second Military Medical University, Shanghai, China. 4. Dr David Evans, Avon Longitudinal Study of Parents and Children, Bristol, UK. 5. Assoc. Prof Andreas Zankl, The University of Queensland Centre for Clinical Research, Australia 6. Professor John Eisman, Garvan Institute of Medical Research, Sydney, Australia. 7. Professor Andrei Uitterlinden, Erasmus University, Rotterdam, Holland. 8. Professor Jon Tobias, University of Bristol, UK. 9. Professor Udo Opperman, Structural Genomics Consortium, University of Oxford, UK. 10. Professor Perry Bartlett, Queensland Brain Institute, The University of Queensland, Australia 11. Professor Bryan Mowry, Queensland Brain Institute, The University of Queensland, Australia 12. Professor Jamie Craig and Dr Kathryn Burdon, Department of Ophthalmology, Flinders University, Adelaide, Aus.

Dr Ray Steptoe 1. Professor John Upham, The University of Queensland, Brisbane, Australia 2. Dr Janet Davies, The University of Queensland, Brisbane, Australia 3. Dr Harry Parekh, The University of Queensland, Brisbane, Australia 4. Professor Geoff Hill, Queensland Institute for Medical Research, Brisbane Australia 5. Assoc. Professor Toby Coates, Queen Elizabeth Hospital, Adelaide, Australia 6. Assoc. Professor Phil Hansbro, University of Newcastle, Newcastle, Australia. 7. Prof. Tim Sparwasser, Zentrum für Experimentelle und Klinische Infektionsforschung, Hannover, Germany

Dr Gethin Thomas 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

52

Professor Ranjeny Thomas, UQDI. Professor Malcolm Smith, Flinders Medical Centre, South Australia. Dr Fernando Pimentel-Santos, Faculdade de Ciências Médicas da Universidade Nova de Lisboa, Lisboa, Portugal. Dr Roman Fischer and Professor Paul Bowness. Centre for Cellular and Molecular Physiology, Nuffield Department of Clinical Medicine, Oxford University. Dr Allison Pettit, The University of Queensland. Dr Martin Rudalweit and ASAS (Assessment of spondyloarthritis International Society). Dr Manuel Fernandez-Rojo, IMB, UQ Dr Gary Leong, IMB, UQ Dr Michaela Kneissel, Director Bone Metabolism Research, Musculoskeletal Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland. Professor Tibor Glant, Professor, Director, Section of Molecular

11.

Medicine, Department of Orthopedic Surgery, Rush University Medical Center, Chicago, USA. Raj Thakker, May Professor of Medicine, Academic Endocrine Unit, Nuffield Department of Clinical Medicine, University of Oxford, UK.

Professor Ranjeny Thomas 1. Professor Barbara Fazekas de St Groth, Centenary Institute, Sydney 2. Professor Thomas Marwick, UQ 3. Dr Andrew Cotterill, Dr Mark Harris, Dr Pati Gallego, Mater Health Services 4. Dr Anthony Purcell, Uni Melbourne 5. Dr Phil Hansbro, Uni of Newcastle 6. Professor Andrew Cope, Kings College, London 7. Professor Jamie Rossjohn, Dr Hugh Reid, Monash University 8. Professor Shimon Sakaguchi, University of Osaka, Japan 9. Dr Srinivas Mutalik, Manipal University, India 10. Dr Kevin Deane, University of Colorado 11. Dr Roland Steck, QUT 12. Dr Allison Pettit, UQ 13. Dr Bob Wilson, Qld Health Pathology Services 14. Dr Kristine Kikly, Dr Jonathan Sedgwick, Dr Julian Davies, Eli-Lilly, USA 15. Dr Mireille Lahoud, WEHI, Melbourne 16. Dr Helen Thomas and Prof Tom Kay, St Vincents Institute, Melbourne

Dr Antje Blumenthal 1. 2. 3. 4. 5. 6.

Assoc/Professor Christine Wells, The University of Queensland Dr Bernadette Saunders, Centenary Institute, Sydney Professor Christopher Karp, Cincinnati Children’s Hospital Medical Center, USA Professor Matthias Ernst, Ludwig Institute, Melbourne Professor Richard Lang, Cincinnati Children’s Hospital Medical Center, USA Professor Robert Capon, The University of Queensland

Dr Marcel Dinger 1. Ranjan Perera, Sanford-Burnham Medical Research Institute, Florida. 2. John Stamatoyannopoulos, University of Washington, Seattle. 3. Colleen Nelson, QUT 4. Melissa Brown, The University of Queensland. 5. John Rinn, Harvard University, Boston. 6. Thomas Gingeras, Cold Spring Harbor Laboratories, New York. 7. Jeff Jeddeloh, Roche Nimblegen, Inc., Wisconsin. 8. Dagmar Wilhelm, The University of Queensland. 9. Andrew Perkins, The University of Queensland. 10. Tao Liu, Lowy Cancer Research Centre, University of NSW.

Professor Ian Frazer 1. 2. 3. 4. 5.

Mark Kendall – AIBN Manuel Ferreria – QIMR Paul Lambert – McArdle Institute , Madison, Wi. Silvia Francesci – IARC Freddy Sitas, Sydney


6. (International consortium, locally Matt Brown) 7. Prof Peter Soyer, School of Medicine 8. Len Tarivonda, Director of Public Health, Vanuatu

Associate Professor Brian Gabrielli 1. Professor Sean Grimmond, IMB, The University of Queensland 2. Associate Professor Rick Sturm, IMB, The University of Queensland 3. Professor Peter Soyer, Dermatology, The University of Queensland 4. Dr Graeme Walker, QIMR 5. Dr Duncan Lambie, PA Hospital 6. Dr Nicole Cloonan, IMB, The University of Queensland 7. Prof Grant McArthur, Peter MacCallum Cancer Institute 8. A/Prof Rick Pearson, Peter MacCallum Cancer Institute 9. Dr Cheryl Napier, Array Biopharma, Boulder CO. USA 10. Dr Helen Rizos, Westmead Cancer Institute, Sydney 11. Dr Nikolas Haass, Centenary Institute, Sydney

Veterinary Science, The University of Queensland 8. Prof Judith Clements, Prof Colleen Nelson, Prof Pamela Russell, Prof Dietmar Hutmacher, Dr Patrick Ling, Australian Prostate Cancer Research Centre – Qld, IHBI QUT 9. Dr Kim-Anh Le Cao, Dr Melissa Davis, Queensland Facility for Advanced Bioinformatics 10. Dr David Chen, School of Communication and Information Technology, Griffith University 11. Prof David Whiteman, Prof Nick Hayward, Dr Derek Nancarrow, QIMR 12. A/Prof Nick Saunders, A/Prof Brian Gabrielli, UQDI

Dr Graham Leggatt 1. 2. 3. 4. 5.

Dr. Joanne Blanchfield, The University of Queensland Prof. Paul Burn, The University of Queensland Prof. Phil Hugenholtz, The University of Queensland Dr. Ben Panizza, Princess Alexandra Hospital Associate Professor Dale Godfrey, University of Melbourne

Professor Tom Gonda

Associate Professor Nigel McMillan

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

1. 2. 3. 4. 5. 6. 7. 8.

A/ Prof Robert Ramsay, Peter MacCallum Cancer Centre, Melbourne, Australia Prof Richard D’Andrea, Centre for Cancer Biology/SA Pathology and The Queen Elizabeth Hospital, Adelaide, Australia A/Prof Brian Gabrielli, Diamantina Institute, The University of Queensland, Brisbane, Australia Dr Paul Leo, Diamantina Institute, The University of Queensland, Brisbane, Australia A/Prof Mark Smythe, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia A/Prof Andrew Perkins, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia Dr Glenn Francis, Princes Alexandra Hospital, Brisbane, Australia A/Prof Paula Marlton and A/Prof Devinder Gill, Princes Alexandra Hospital, Brisbane, Australia Dr Geoff Sjollema and Mr Rob Tunningley, Australian Phenomics Facility, Australian National University, Canberra, Australia Dr Evgeny Glazov, Diamantina Institute, University of Queensland, Brisbane, Australia Dr Brooke Gardiner, Diamantina Institute, The University of Queensland, Brisbane, Australia A/Prof Jean-Pierre Levesque and Dr Ingrid Winkler, Mater Medical Research Institute, Brisbane, Australia

Dr Michelle Hill 1. 2. 3. 4. 5. 6. 7.

Prof Robert Parton, Prof Alpha Yap, Prof Rohan Teasdale, Dr Melissa Davis, IMB, UQ Dr Marie- Odile Parat, School of Pharmacy, UQ Dr Janet Davies, SOMS, UQ Prof Robert Nabi, Associate Professor Leonard Foster, University of British Columbia, Vancouver, Canada Dr Peter Mollee, Dr Patricia Renault, Pathology Queensland, PAH Prof James W Dennis, Canada Research Chair, Senior Investigator & Professor, Department of Molecular Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Samual Lunenfeld Research Institute, Canada Dr Caroline O’Leary, Dr Helle Bielefeldt-Ohmann, School of

Dr Johannes Fruehauf, AuraBiosciences and Harvard Medical School, Boston, USA Dr Michael Monterio, AIBN, The University of Queensland, Brisbane, Australia Dr Harry Parehk, Department of Pharmacy, The University of Queensland, Brisbane, Australia Dr Mark Belhke, International DNA Technologies, Iowa, USA Prof Bryan Williams, Monash University, Melbourne, Australia Associate Professor Thomas Preiss, Victor Chang Institute, Sydney, Australia Professor Jack Bennink and Jon Yewdell, National Institute of Allergy and Infectious Disease, USA Prof Mark Kendall, The University of Queensland Drs Tim Doran and Linfa Wang, CSIRO

Dr Ali Naderi 1. 2. 3.

Professor Sunil Lakani, The University of Queensland Centre for Clinical Research Dr. Glenn Francis, Pathology Queensland Dr. Luke Hughes-Davies, Department of Oncology, University of Cambridge, UK

Dr Fiona Simpson 1. Professor Roger Daly, The Garvan Research Institute, Sydney, Australia 2. Professor Hani Gabra, Professor of Medical Oncology, Imperial College London, UK 3. Professor H. Peter Soyer, Princess Alexandra Hospital and UQ, Brisbane, Australia 4. Professor Jesse Martinez, Chief Scientific Officer, Arizona Cancer Center. USA 5. A. Professor Sandro Porceddu, Princess Alexandra Hospital and UQ, Brisbane, Australia 6. Professor Brian Burmeister, Princess Alexandra Hospital and UQ, Brisbane, Australia 7. Dr Mathew Foote, Princess Alexandra Hospital and UQ, Brisbane, Australia

53


Granting Bodies and Donors The University of Queensland Diamantina Institute thanks its benefactors who partner us in research. Abbott Australasia http://www.abbottaustralasia.com.au/

National Health and Medical Research Council http://www.nhmrc.gov.au/

Arthritis Foundation of Australia http://www.arthritisaustralia.com.au/

National Institutes of Health http://grants.nih.gov/grants/oer.htm

Arthritis QLD http://www.arthritis.org.au/

PA Research Foundation http://www.pafoundation.org.au/

Association for International Cancer Research http://www.aicr.org.uk/

Perpetual Trustees http://www.perpetual.com.au/philanthropic-services.aspx

Australian Cancer Research Foundation http://www.acrf.com.au/

Prostate Cancer Foundation of Australia http://www.prostate.org.au/articleLive/

Australian Research Council http://www.arc.gov.au/

Queensland Government, Department of Employment, Economic Develoopment and Innovation. http://www.sd.qld.gov.au/dsdweb/v4/apps/web/ contentcfm?id=8212

Brain Foundation http://brainfoundation.org.au/ Cancer Council Queensland http://www.cancerqld.org.au/ Juvenile Diabetes Research Foundation International http://www.jdrf.org/ Leukaemia Foundation www.leukaemia.org.au/ Lions Medical Research Foundation http://www.lionsq3.org.au/index.php/projects/ 69-health-projects/120-lmrf.html National Breast Cancer Foundation www.nbcf.org.au/

54

Queensland Government, Queenland Health, Cancer Collaborative Group, PA Hospital http://www.health.qld.gov.au/pahospital/ research/ccg_default.asp Sanofi Aventis http://www.sanofi-aventis.com.au/l/au/en/index.jsp The University of Queensland http://www.uq.edu.au/ Uniquest https://www.uniquest.com.au/ Wesley Research Institute Ltd http://www.wesleyresearch.org.au/


Grants CIA Granting Body Grant Grant title Type

Comm- Total TOTAL $ enced yrs

Ali Naderi PA Research Foundation Project

PA Research Foundation Private Practice Trust Fund Research Support Grants-A pre-clinical Study of Combined Androgen Receptor and MEK inhibition as a targeted therapy in Molecular Apocrine Breast Cancer

1/01/11

1

$75,000.00

Ali Naderi

Translational Phase 2 Clinical Trial of Combined 1/01/09 Androgen Receptor and ErbB2 Inhibition in Molecular Apocrine Subtype of Breast Cancer

2

$100,000.00

Queensland Government, Project Queenland Health, Cancer Collaborative Group, PA Hospital

Angus Australian Research Council Project Discovery Project- Multiscale stochastic Harding, (ARC) modelling of tumour robustness Tianhai Tian

1/01/10

3

$240,000.00

Angus Harding, Brain Foundation Project Brian Gabrielli, S Olson

Targeting the G2 phase checkpoint in Glioblastoma to improve the efficacy of current therapy

1/01/11

1

$30,000.00

Angus Harding, B Reynolds, Brian Gabrielli

The role of tumour-initiating cells in glioma

1/01/09

3

$116,500.00

Angus Harding The University of Queensland Award Foundation Research Excellence Award - The role of the mutator phenotype in the evolution of adult brain tumour therapy resistance.

19/09/11

2

$60,000.00

Anne-Sophie The University of Queensland Fellowship Bergot

01/01/11

3

$289,328.00

Antje The University of Queensland Fellowship UQ Postdoctoral Research Fellowship: Blumenthal The role of Wnt proteins in inflammation

01/01/10

3

$145,000.00

Antje Blumenthal

Early Career Researcher Award

1/01/11

2

$28,000.00

Synthetic lethality screen targeting a defective checkpoint in melanoma.

1/01/10

2

$200,000.00

01/01/10

5

$560,000.00

National Health and Medical Research Council (NHMRC)

Project

The University of Queensland Project

Brian Gabrielli, Cancer Council Queensland Project N Waterhouse, Kelly Brooks, R Johnstone Brian Gabrielli

National Health and Medical Research Council (NHMRC)

Postdoctoral Research Fellowship - Skin immune sentinels: roles and functions of immunoregulatory T cells in HPV16 skin infection in mice

Fellowship Senior Research Fellowship

Gethin Thomas, National Health and Medical Project Marcel Dinger, Research Council (NHMRC) M Pheasant, Brooke Gardiner

Regulatory RNAs underlying genetic associations with ankylosing spondylitis

01/01/10

3

$416,575.00

J Stankovich, V Perreau, Evgeny Glazov, B McMorran, B Taylor, S Browning

Identifying rare genetic variants conferring susceptibility to multiple sclerosis

1/01/10

2

$65,429.00

02/02/09

4

$477,500.00

30/04/10

1

$12,000.00

National Health and Medical Project Research Council (NHMRC) (Awarded to Menzies Institute, University of Tasmania)

Fiona Simpson National Health and Medical Fellowship CDA-Biomedical (R. Douglas Wright Research Council (NHMRC) Biomedical CDA)- Endosomal tubule formation in health and disease Fiona Simpson The University of Queensland Project

New Staff Research Start-Up Fund; Growth factor signalling in health and squamous cell carcinoma.

55


Grants cont. CIA Granting Body Grant Grant title Type

Comm- Total TOTAL $ enced yrs

Gethin Thomas Lions Medical Research Fellowship New therapies for bone and joint disease Foundation through identification of novel disease causing genes

1/04/08

3

$300,000.00

Gethin Thomas National Health and Medical Project Research Council (NHMRC)

The immunogenetics of ankylosing spondylitis: a genetic and functional investigation of IL23R and related genes

1/01/09

3

$456,531.00

Gethin Thomas, National Health and Medical Project A Pettit Research Council (NHMRC)

Novel treatment approaches to prevent joint fusion in ankylosing spondylitis

01/01/11

3

$461,473.00

Graham Leggatt, Cancer Council Queensland Project Nicholas Saunders

Suppressor NKT cell trafficking to epithelial precancer

1/01/10

2

$182,500.00

Merja Ruutu Cancer Council Queensland Project

Investigating the mechanisms by which immune cells (particularly T cells and NKT cells) target and eliminate cells expressing tumour antigens.

01/01/11

2

$194,788.00

P Lambert, NIH (Awarded to University Project Ian Frazer of Wisconsin)

Novel Interventions Against HPV-associated Neoplasia ( NCI-MMHCC-Integration of mouse models into human cancer research)

1/01/09

5

$1,154,000.00

Ian Frazer Perpetual Trustees Fellowship Fellowship in skin cancer research in Queensland

01/07/09

5 $1,000,000.00

Ian Frazer

01/01/07

5

$2,750,000.00

Ingrid Hickman Lions Medical Research Fellowship Obesity-related inflammation and insulin Foundation resistance in chronic liver disease: Exercise and diet as treatment options

1/04/09

3

$300,000.00

Ingrid Hickman

Obesity-related inflammation and insulin resistance in chronic liver disease: exercise and diet as treatment options

1/01/08

3

$413,600.00

John D Reveille, NIH (Awarded to) Project Matthew Brown University of Texas

PO1 Project 1 -Genetic Factors in Ankulosing spondylitis

1/01/06

5

$1,747,148.00

John D Reveille, NIH (Awarded to University Project Matthew Brown of Texas + Cedars-Sinai)

PO1 Project 2-Genetics and ankylosing spondylitis (AS) pathogenesis

1/01/09

3

$50,000.00

Kerry Inder

The University of Queensland Award

Early Career Researcher Award

1/01/11

1

$24,000.00

Marcel Dinger

National Health and Medical Fellowship Career Development Award- Noncoding Research Council (NHMRC) RNAs in neural stem cell differentiation

1/01/10

4

$397,000.00

1/08/09

5

$192,000.00

01/01/07

5

$651,250.00

QLD Government Department Fellowship of Employment, Economic Development and Innovation

National Health and Medical Project Research Council (NHMRC) *extended into 2011

Marcel Dinger QLD Government Department Fellowship of Employment, Economic Development and Innovation Matthew Brown

56

National Health and Medical Research Council (NHMRC)

Innovation Skills Fund Smart State 2005-06 Premierâ&#x20AC;&#x2122;s Fellowship

Smart Futures Fellowship: Functional screening of long noncoding RNAs: novel insights into the molecular basis of mammalian development and disease

Fellowship Research Fellowship

Matthew Brown Sanofi-Aventis Australia Project Pty Ltd

Project 1 - A randomised double blind- placebo controlled dose ranging study to evaluate the efficacy and safety of SAR 153191 in patients with Ankylosing Spondylitis (AS)

1/12/09

3

$150,000.00

Matthew Brown Sanofi-Aventis Australia Project Pty Ltd

Project 2 - A multicenter uncontrolled extension study evaluating the long term safety and efficacy of SAR153191 in patient with Ankylosing Spondylitis (AS)

20/08/10

5

$200,000.00


CIA Granting Body Grant Grant title Type

Comm- Total TOTAL $ enced yrs

Matthew Brown, National Health and Medical Huji Xu, Research Council (NHMRC) David Evans

Project

MHC Genetics of Ankylosing spondylitis

1/01/09

3

$547,263.00

Matthew Brown, National Health and Medical Project Huji Xu, Research Council (NHMRC) Gethin Thomas

The immunogenetics of ankylosing spondylitis: a genetic and functional investigation of IL23R and related genes

1/01/09

3

$521,750.00

Matthew Brown, Australian Research Project Huji Xu, Council (ARC) Perry Bartley, Robyn Wallace, Peter Visscher, Bryan Mowry, David Reutens

Linkage Project- Sino-Australian Neurogenetics Initiative

01/07/11

4

$690,000.00

Matthew Brown, John Eisman, Graeme Jones, Geoffrey Nicholson, Richard Prince, Ego Seeman

Project

GEFOS - Genetic Factors for Osteoporosis

1/01/08

4

$800,000.00

Matthew Brown, Arthritis Foundation of Project Tony Merriman, Australia Maureen Rischmueller, Malcolm Smith, Andrew Harrison, Bain Shenstone

Genetic and functional characterisation of ERAP1 variants associated with ankylosing spondylitis

1/01/11

1

$50,000.00

Veronique PA Research Foundation Project Chachay, Ingrid Hickman

The role of resveratrol in the management of non-alcoholic fatty liver disease (NAFLD)

1/02/11

1

$25,000.00

National Health and Medical Research Council (NHMRC)European Union Helath Collaborative Grant

Michelle Hill, Ian Frazer, Brian Gabrielli, Nigel McMillan, Antje Blumenthal

The University of Queensland Equipment Laser Scanner for Biomolecular Imaging /NHMRC

1/01/11

1

$70,758.00

Michelle Hill, C Nelson, R Parton, S Lee

The Association for Project International Cancer Research

Modulating cholesterol-dependent lipid rafts and caveolin in prostate cancer therapy

01/01/10

3

$306,051.50

Michelle Hill National Health and Medical Fellowship CDA, Biomedical-Molecular mechanisms Research Council (NHMRC) underlying the positive associations between male gender & leptin with Barrettâ&#x20AC;&#x2122;s oesophagus

01/01/09

4

$390,000.00

Michelle Hill, Prostate Cancer Project R Parton, Foundation Australia L Chopin

Young Investigator Grant- A systems biology approach to eluciadte the molecular mechanisms of caveolin-1 and statins in prostate cancer progression and metastasis

01/01/09

4

$331,264.00

Michelle Hill, The University of Queensland Project H Bielefeldt- Ohmann

UQ Collaboration and Industry Engagement Fund-Using comparative oncology to discover susceptibility genes and diagnostic biomarkers for angiosarcoma

11/11/10

1

$75,000.00

Nicholas Saunders

A novel tumour supressor function for E2F7 in squamous cell carcinoma

01/01/09

3

$503,625.00

The role of osteoclasts in the development of osteosarcoma metastases

1/01/10

2

$133,334.00

National Health and Medical Project Research Council (NHMRC)

Nicholas Cancer Council Queensland Project Saunders, A Evdokiou, D Thomas

57


Grants cont. CIA Granting Body Grant Grant title Type Scott Sommerville, Liliana Monoz, Nicholas Saunders

Wesley Research Institute Project Limited

Development of nanoparticle mucosal delivery 01/01/11 systems for siRNA-based cancer therapies

2

$178,000.00

Nigel McMillan, T Preiss, Raymond Steptoe

National Health and Medical Research Council (NHMRC)

RNAi and the Immune System

01/01/10

3

$550,500.00

M Monteiro, Nigel McMillan,

Australian Research Council Project (ARC) (Awarded to AIBN)

Engineered Polymer Nanoparticles: A Potent Weapon Against Cancer

1/01/09

3

$90,000.00

Nigel McMillan

UniQuest

Project

Pathfinder- CoaTED ldh FOR ranI DELIVERY

1/04/10

1

$32,550.00

Devinder Gill, Nigel McMillan

Leukaemia Foundation (Awarded to QLD Health, PAH Devinder Gill)

Project

Grant-in-Aid

1/01/10

2

$60,000.00

20/06/11

1

Ian Frazer et al Australian Research Council (ARC) (Awarded to QUT)

58

Comm- Total TOTAL $ enced yrs

Project

Infrastructure Comprehensive cell imaging facility and Equipment

Ping Ye The University of Queensland Fellowship

Postdoctoral Research Fellowship- Identification and development of inhibitors of the Myb oncoprotein

1/01/09

3

$20,000.00

Purnima Bhat The University of Queensland Fellowship

Local enhancement of effector T cell functions 1/01/09 in suppressing epithelial tumour development.

3

$75,500.00

Ranjeny Thomas Australian Research Council Fellowship (ARC)

Future Fellowship Understanding and regulating 01/07/09 autoimmune disease through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) family transcription factor, RelB

4

$1,782,400.00

Ranjeny Thomas Arthritis Queensland

Professorial Chair

1

$105,000.00

Other -

1/01/11

Ranjeny Thomas Juvenile Diabetes Research Project Foundation International

nPOD Research Projects- Pathological changes 01/05/10 associated with chronic RelB activation in T1D

1+ $112,000.00

Ranjeny Thomas, Juvenile Diabetes Research Project John Prins, Foundation International Matthew Brown

RelB response as a biomarker of diabetes susceptibility

1/01/08

4

$507,422.00

Ranjeny Thomas, National Health and Medical Program Geoff Hill, Research Council (NHMRC) Ian Frazer, Matthew Brown, Mariapia Degli-Esposti

Program Grant- Immunological therapies for cancer, chronic infection and autoimmunity

01/01/10

5

$10,130,000.00

Ranjeny Thomas, National Health and Medical Dennis Dowhan Research Council (NHMRC)

India Institutional Engagement Strategy

1/01/11

1

$20,000.00

Merja Ruutu, Arthritis Foundation of Australia Project Ranjeny Thomas, Matthew Brown

Targeted Immunotherapy in the SKG model of inflammatory arthritis

1/01/11

1

$40,000.00

Shayna Street

National Health and Medical Fellowship Research Council (NHMRC)

Peter Doherty Fellowship- The role of RelB in atopic asthma

1/01/07

5

$297,312.00

Raymond Steptoe

National Health and Medical Project Research Council (NHMRC)

Mechanisms of rapid memory CD8+ T-cell inactivation

01/01/11

3

$307,524.00

Other


CIA Granting Body Grant Grant title Type

Comm- Total TOTAL $ enced yrs

Raymond Steptoe

Juvenile Diabetes Research Project Foundation International

1/03/08

3

$450,000.00

Raymond Steptoe

National Health and Medical Fellowship Biomedical CDA- Tolerance induction by Research Council (NHMRC) antigen-presenting cell-targeted antigen

1/01/08

4

$429,000.00

Stephen Blake The University of Queensland Fellowship UQ Postdoctoral Research Fellowship: 01/01/10 Enhancing adaptive immune responses against tumour cells through targeted RNA interference

3

$258,000.00

Sunny Liu

02/10/08

3

$215,000.00

Induction of tolerance in memory diabetogenic T cells

National Health and Medical Fellowship Australia-China Exchange Fellowship, Research Council (NHMRC) T cell trafficking and effective immunotherapy *extended into 2011 for cancer

Thomas Gonda, National Health and Medical Project G Goodall, P Leo, Research Council (NHMRC) S Barry

A comprehensive analysis of Myb target genes involved in myelopoiesis and myeloid transformation

1/01/09

3

$491,250.00

Thomas Gonda, The Association for International Project R Ramsay Cancer Research

MYB regulation of differentiation and apoptosis in breast cancer: Targets and targeting

01/01/10

3

$558,236.00

Thomas Gonda, Australian Research Council Project R Ramsay, (ARC) M Brown

The MYB gene as a model for global transcriptional regulation: stopping, starting and looping

1/01/09

3

$240,000.00

A Yap, E Thompson, G Goodall, C Saunders, R Anderson, I Street, K Stanley, A Dowling, Thomas Gonda

Targeting breast cancer recurrence through epithelial mesenchymal plasticity

1/03/11

5

$45,000.00

Won Jae Lee National Health and Medical Fellowship NHMRC Training (Postdoctoral) Fellowship- 1/01/07 Research Council (NHMRC) Mechanisms regulating cell cycle progression in response to UV radiation

5

$407,554.00

Won Jae Lee

“National Breast Cancer Project Foundation (Awarded to St Vincent’s Institute of Medical Research)”

The University of Queensland Award

Early Career Researcher Award

1/01/11

1

$20,000.00

Theoretical Population Genetics

1/10/11

1

$65,343.00

1/01/10

5

$1,098,317.00

Peter Visscher National Institutes of Health (NIH)

Program

Peter Visscher

National Health and Medical Research Council (NHMRC)

Fellowship NHMRC Research Fellowship (SPRF)

Peter Visscher, M Goddard

National Health and Medical Project Research Council (NHMRC)

Explaining the Dark Matter of Genome-wide Association Studies for Complex Disease

1/01/10

2

$264,750.00

Allan McRae, J Painter

National Health and Medical Research Council (NHMRC)

Inheritance of DNA methylation state in humans 1/01/11

3

$579,766.00

3

$487,769.00

Project

Raymond Steptoe The University of Queensland Fellowship Vice Chancellor’s Senior Research Fellowship-Terminating autoimmune diabetes

on hold to start 2016

59


Financials 2011 External Funding, Fellowships and Scholarships Abbott Australasia Pty Ltd

2% 66,974

Arthritis Australia

159,117

Arthritis Queensland

105,000

Association for International Cancer Research

218,809

Australian Research Council

537,198

Brain Foundation International Agency for Research on Cancer Juvenile Diabetes Research Foundation International

30,000

Lions Medical Research Foundation

125,000 332,117

PA Research Foundation

170,208 124,262

Queensland Government

333,000

Queensland Health

126,709

Perpetual Trustees

200,000 49,000 21,000

The Cancer Council Queensland

485,520

UniQuest Pty Limited

114,659

Wesley Research Institute

Maintenance Salaries Travel

7%

11,500

Prostate Cancer Foundation of Australia

The Cancer Council NSW

Equipment

4,669,667

National Institutes of Health

Sanofi-Aventis Australia Pty Ltd

35%

5,901 60,000

Pfizer Australia Pty Ltd

The UQ Diamantina Institute Expenditure

138,253

Leukaemia Foundation of Australia National Health and Medical Research Council

45%

18%

75,000

8,158,893

36% Grant and Funding Source

57% ARC NHMRC Other

60


Occupation Health and Safety by Dr Juan Cooper, Chair UQDI Safety Committee

Occupational Health and Safety (OH&S) at The University of Queensland Diamantina Institute (UQDI) is facilitated by the Infrastructure Manager, Workplace Health and Safety Officer and Floor Managers, who together provide a comprehensive framework of training including induction of all new staff, refresher training, auditing of risk assessments for experimental processes and monitoring of all research practices. The UQDI Safety Committee meets four times a year to review all areas of safety and propose measures to management to ensure regulatory compliance to assist in the promotion of a safe work environment. 2011 Highlights

Challenges ahead in 2012

> 2010 Internal OH&S Management System and Auditing Program - actions completed

> Education and training of supervisory staff in OH&S responsibilities

> OH&S Goals Review for 2010 - completed > UQDI Workplace Assessment Checklist for 2011 - completed

> Regular auditing and updating of information contained in the risk assessment database

> Eye Protection Policy - approved as a mandatory requirement for laboratory work

> Harmonisation of UQDI safety training documentation with TRI OH&S policies

> Tissue Culture Facility guidelines - updated and approved

> Maintaining a safe working environment during the transition into TRI

> Health & Safety Management Plan 2011 - reviewed and approved > Annual OGTR internal audit for 2011 - good overall compliance achieved > Audit of Incident Reports - all approved or closed off There were a small number of minor OH&S incidents in 2011. The bulk of injuries and incidents in the past year related to laboratory work and included chemical spills, splashes or handling incidents, repetitive strain injuries, trips, falls, cuts and abrasions. Whilst all were minor and small in number, it is important to ensure that all staff members are regularly reminded of the importance to follow approved protocols and wear personal protective equipment. Of particular importance is the vulnerability of staff to eye injury. Considerable discussion and consultation throughout the year has focused on minimising the risk of eye injury to our staff through education, training and the provision of personal protective equipment. An increased focus on OH&S responsibilities of both staff and supervisors has helped in the continuing development of a â&#x20AC;&#x153;safety cultureâ&#x20AC;? at UQDI. These responsibilities are now seen as an important part of annual staff appraisals and in professional development of staff. With the impending move of all UQDI staff to the new Translational Research Institute (TRI) building in late 2012, it was timely that all work processes be reviewed. Considerable effort was put into updating risk assessments and streamlining all induction procedures.

61


DIAMANTINA INSTITUTE â&#x20AC;&#x153;turning scientific discoveries into better treatmentsâ&#x20AC;?

The University of Queensland Diamantina Institute Research Wing, Building 1 Princess Alexandra Hospital Ipswich Road, Woolloongabba, QLD 4102, Australia Phone +61 7 3176 5944 Email di.enquiries@uq.edu.au Web www.di.uq.edu.au The University of Queensland Diamantina Institute thanks our benefactors who partner us in research.

UQ Diamantina Institute Annual Report 2011  
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