Novel bioinformatics approaches for biological inference from comparative genomics data. Unlocking the potential of the human and other genome sequences depends almost entirely upon comparative genomics techniques. We will develop powerful bioinformatic models, implemented as high-performance computing solutions, for the examination of gene sequences. Improving these models, which represent the initial building block for all comparative genomics techniques, will be beneficial across genomics dep ....Novel bioinformatics approaches for biological inference from comparative genomics data. Unlocking the potential of the human and other genome sequences depends almost entirely upon comparative genomics techniques. We will develop powerful bioinformatic models, implemented as high-performance computing solutions, for the examination of gene sequences. Improving these models, which represent the initial building block for all comparative genomics techniques, will be beneficial across genomics dependent industries. A major outcome from this work will be an integrated software/hardware product optimised for statistical examination of very large-scale genomics data.Read moreRead less
Molecular response to interferon beta treatment in multiple sclerosis. Inteferon beta (IFNb) is the frontline drug for treatment of multiple sclerosis. However, in many patients this expensive drug provides no benefit, resulting in unnecessary, uncontrolled disease progression, and in a waste of many millions of dollars each year. A common explanation for this treatment failure is the development of neutralising antibodies (NABs). We will establish the prevalence and effects of NABs in Austra ....Molecular response to interferon beta treatment in multiple sclerosis. Inteferon beta (IFNb) is the frontline drug for treatment of multiple sclerosis. However, in many patients this expensive drug provides no benefit, resulting in unnecessary, uncontrolled disease progression, and in a waste of many millions of dollars each year. A common explanation for this treatment failure is the development of neutralising antibodies (NABs). We will establish the prevalence and effects of NABs in Australian patients, use novel techniques to identify biomarkers for IFNb response, evaluate the diagnostic and therapeutic value of the biomarkers, and develop a new test for NABs. Tailored use of this drug, and possible new therapeutic targets, will result, benefiting the patient and community.Read moreRead less
Dairy Milk Phospholipids in the Prevention of Atherosclerosis. The present project is expected to provide novel information pertaining to the separation of phospholipid (PL) fractions from buttermilk. In addition, it will generate scientific/medical knowledge concerning the use of dietary PL preparations in the prevention of arterial atherosclerosis. Together, this innovative research will help support the commercial development of PL separation from buttermilk. It will also lay the ground-wo ....Dairy Milk Phospholipids in the Prevention of Atherosclerosis. The present project is expected to provide novel information pertaining to the separation of phospholipid (PL) fractions from buttermilk. In addition, it will generate scientific/medical knowledge concerning the use of dietary PL preparations in the prevention of arterial atherosclerosis. Together, this innovative research will help support the commercial development of PL separation from buttermilk. It will also lay the ground-work for additional studies into the therapeutic benefit of dietary PLs and the commercialization of milk PL as a nutraceutical or functional food. The present project thus has significant academic, commercial and therapeutic value of potential benefit to all Australians.Read moreRead less
Transfer ribonucleic acid (tRNA) synthetases as drug targets in Plasmodium falciparum. Malaria is a major worldwide infectious disease. The disease kills around 2 million people every year, and current drugs are increasingly failing due to parasite drug resistance, creating an urgent demand for new drugs, that inhibit different targets. The Fellow will study a new class of parasite drug targets, the transfer ribonucleic acid (tRNA) synthetase enzymes to find novel inhibitors. Compounds blocking ....Transfer ribonucleic acid (tRNA) synthetases as drug targets in Plasmodium falciparum. Malaria is a major worldwide infectious disease. The disease kills around 2 million people every year, and current drugs are increasingly failing due to parasite drug resistance, creating an urgent demand for new drugs, that inhibit different targets. The Fellow will study a new class of parasite drug targets, the transfer ribonucleic acid (tRNA) synthetase enzymes to find novel inhibitors. Compounds blocking these enzymes may lead to new drugs to combat malaria.Read moreRead less
Structure-based inhibitor design of VAP-1/SSAO for the treatment of respiratory dirsorders and other major inflammatory diseases. Inflammatory diseases, such as asthma, rheumatoid arthritis and multiple sclerosis, are widespread and often poorly treated in Australia and elsewhere. Inhibitors of the recently studied VAP-1/SSAO protein are predicted to effectively treat the inflammation symptoms of one or more of these diseases. A structure-based approach to discover these new medicines should pro ....Structure-based inhibitor design of VAP-1/SSAO for the treatment of respiratory dirsorders and other major inflammatory diseases. Inflammatory diseases, such as asthma, rheumatoid arthritis and multiple sclerosis, are widespread and often poorly treated in Australia and elsewhere. Inhibitors of the recently studied VAP-1/SSAO protein are predicted to effectively treat the inflammation symptoms of one or more of these diseases. A structure-based approach to discover these new medicines should provide a means to identify patentable compounds, with high potency, efficacy and safety. If this approach is successful, an Australian pharmaceutical company will be one of the first to the market with this new medicine to treat these chronic diseases.Read moreRead less
New analgesics based on µ-conotoxins: structure-based design of helical mimetics. Diseases in which voltage-gated sodium channels are implicated are contributors to morbidity and mortality in the Australian population, and this project promises to provide new leads for the future development of drugs to treat such diseases, in particular analgesics for the treatment of chronic pain. The generation of these leads will entail the development of new approaches to mimicking key regions of peptides a ....New analgesics based on µ-conotoxins: structure-based design of helical mimetics. Diseases in which voltage-gated sodium channels are implicated are contributors to morbidity and mortality in the Australian population, and this project promises to provide new leads for the future development of drugs to treat such diseases, in particular analgesics for the treatment of chronic pain. The generation of these leads will entail the development of new approaches to mimicking key regions of peptides and proteins in drug-like molecules. This is a highly interdisciplinary project, spanning structural biology, molecular design, medicinal chemistry, molecular biology and electrophysiology, and the training of PhD graduates with such broad experience represents another national benefit of the project.Read moreRead less
Identification of novel antigens for vaccination and immunotherapy against the human gastric pathogen, Helicobacter pylori. The bacterium Helicobacter pylori is a significant human pathogen which infects the stomach where it is the major cause of stomach and duodenal ulcers, plus two types of cancer. This project proposes to utilise a novel strategy to identify potential vaccine targets on the bacterial surface with the aim to develop an effective vaccine against this organism. Such a vaccine wo ....Identification of novel antigens for vaccination and immunotherapy against the human gastric pathogen, Helicobacter pylori. The bacterium Helicobacter pylori is a significant human pathogen which infects the stomach where it is the major cause of stomach and duodenal ulcers, plus two types of cancer. This project proposes to utilise a novel strategy to identify potential vaccine targets on the bacterial surface with the aim to develop an effective vaccine against this organism. Such a vaccine would protect against the development of stomach cancer, hence saving lives, plus significantly reduce the incidence of stomach ulcers, thereby reducing suffering of individuals and providing financial benefits to employers.Read moreRead less
Antiviral compounds to inhibit the replicase of hepatitis C virus. Hepatitis C virus is a major public health problem. There are currently 200,000 infected individuals in Australia and 16,000 new infections every year. There is no specific treatment and current therapy treats a small percentage of patients only, which consists of interferon-alpha and ribavirin. This results in side effects and only a 50% cure rate. This study's outcomes are expected to lead to greater access to treatment and imp ....Antiviral compounds to inhibit the replicase of hepatitis C virus. Hepatitis C virus is a major public health problem. There are currently 200,000 infected individuals in Australia and 16,000 new infections every year. There is no specific treatment and current therapy treats a small percentage of patients only, which consists of interferon-alpha and ribavirin. This results in side effects and only a 50% cure rate. This study's outcomes are expected to lead to greater access to treatment and improved therapy resulting in higher cure rates and in a dramatic reduction in the cost of treating patients. A novel therapy will provide considerable benefits for the national biotechnology industry.Read moreRead less
Unraveling the genetic networks of cancer development. Cancer causes nearly 30% of all deaths in Australia and the aging of our population means that its incidence will increase for the foreseeable future. The past two decades of cancer research have yielded great advances in identifying the genetic mutations that contribute to cancer, but our understanding of how these mutations cooperate to transform a healthy cell into a tumour cell remains limited. High-throughput genomic analysis of DNA fro ....Unraveling the genetic networks of cancer development. Cancer causes nearly 30% of all deaths in Australia and the aging of our population means that its incidence will increase for the foreseeable future. The past two decades of cancer research have yielded great advances in identifying the genetic mutations that contribute to cancer, but our understanding of how these mutations cooperate to transform a healthy cell into a tumour cell remains limited. High-throughput genomic analysis of DNA from large numbers of tumours is essential to identify and understand the combinations of cancer mutations that are most deadly. Such studies can form the basis for developing better diagnostics and new treatments for patients whose tumours are resistant to current therapies.Read moreRead less
Blood flow routes in muscle. Ageing well, ageing productively. The Australian population is ageing. The proportion of the population over the age of 65 is expected to greatly increase, reaching 22% by the year 2030. The prevalence of type 2 diabetes in this older population is thought to be ~20%, compared to ~6% in younger populations. An initial cause of type 2 diabetes may be microvascular dysfunction brought on by physical inactivity. Therefore this project addresses the concepts of microvasc ....Blood flow routes in muscle. Ageing well, ageing productively. The Australian population is ageing. The proportion of the population over the age of 65 is expected to greatly increase, reaching 22% by the year 2030. The prevalence of type 2 diabetes in this older population is thought to be ~20%, compared to ~6% in younger populations. An initial cause of type 2 diabetes may be microvascular dysfunction brought on by physical inactivity. Therefore this project addresses the concepts of microvascular function and microvascular fitness by using the latest technology to map blood flow routes in muscle under a number of relevant situations. Read moreRead less