Investigation of the function of Sel S a novel selenoprotein. The long term aim of this project is to find a way to prevent or delay the onset of both Type 1 and Type 2 diabetes. ChemGenex pharmaceuticals, our commercial partners have discovered and patented a selenoprotein with antioxidant properties and have shown in vitro that it protects insulin-producing beta cells from oxidative damage. This project aims to prove, in an in vivo setting, that this protein can prevent or delay the onset of d ....Investigation of the function of Sel S a novel selenoprotein. The long term aim of this project is to find a way to prevent or delay the onset of both Type 1 and Type 2 diabetes. ChemGenex pharmaceuticals, our commercial partners have discovered and patented a selenoprotein with antioxidant properties and have shown in vitro that it protects insulin-producing beta cells from oxidative damage. This project aims to prove, in an in vivo setting, that this protein can prevent or delay the onset of diabetes in mouse models of type 1 and Type 2 diabetes.Read moreRead less
Discovery and development of novel insulin sensitising compounds for the treatment of Type 2 diabetes. Diabetes is one of the major health problems facing Australia today, and current treatments are proving inadequate to combat this disease. We previously discovered a new drug with potential for development for the treatment of diabetes. In this project, we will identify how this drug works to combat diabetes in cell and animal models, and use novel chemistry approaches to modify the drug to imp ....Discovery and development of novel insulin sensitising compounds for the treatment of Type 2 diabetes. Diabetes is one of the major health problems facing Australia today, and current treatments are proving inadequate to combat this disease. We previously discovered a new drug with potential for development for the treatment of diabetes. In this project, we will identify how this drug works to combat diabetes in cell and animal models, and use novel chemistry approaches to modify the drug to improve its properties and reduce potential side-effects. The outcomes of this project will be understanding of a new biological process that contributes to the development of diabetes, and the discovery and characterisation of new chemical compounds that could be developed as drugs to treat diabetes.Read moreRead less
Studies on the stereospecific interaction between aldose reductase and inhibitor. There is no therapy specific for treatment of diabetes complications accepted worldwide. The enzyme aldose reductase has shown promising results as a drug target for preventing or delaying the onset of the complications. The structures of human aldose reductase holoenzyme in complex with stereoisomers of the potent inhibitor Fidarestat will be determined at high resolution in order to elucidate the binding modes re ....Studies on the stereospecific interaction between aldose reductase and inhibitor. There is no therapy specific for treatment of diabetes complications accepted worldwide. The enzyme aldose reductase has shown promising results as a drug target for preventing or delaying the onset of the complications. The structures of human aldose reductase holoenzyme in complex with stereoisomers of the potent inhibitor Fidarestat will be determined at high resolution in order to elucidate the binding modes responsible for the differences in their inhibitory potencies. The results may lead to the design of better inhibitors of the enzyme for the treatment of diabetes sufferers, at least until better methods for maintaining metabolic control are developed.Read moreRead less
Structure-based discovery of dipeptidyl peptidase IV inhibitors. Diabetes afflicts approximately 151 million people worldwide, with an estimated increase to 221 million by 2010. To date, no therapy for the treatment of diabetes complications is widely accepted. The enzyme dipeptidyl peptidase IV has shown promising results as a target for the treatment of type 2 diabetes. Structural studies of dipeptidyl peptidase IV in complex with inhibitor will be conducted to elucidate the details of the e ....Structure-based discovery of dipeptidyl peptidase IV inhibitors. Diabetes afflicts approximately 151 million people worldwide, with an estimated increase to 221 million by 2010. To date, no therapy for the treatment of diabetes complications is widely accepted. The enzyme dipeptidyl peptidase IV has shown promising results as a target for the treatment of type 2 diabetes. Structural studies of dipeptidyl peptidase IV in complex with inhibitor will be conducted to elucidate the details of the enzyme-inhibitor interaction. The results will be used to identify the molecular basis of potency and selectivity of dipeptidyl peptidase IV inhibitors and may lead to the discovery of pharmaceutical agents for the treatment of diabetes sufferers.Read moreRead less
Use of a cell based assay to identify novel insulin-sensitising agents. Diabetes and obesity are currently escalating to epidemic proportions in Australia and there is an urgent need to develop new therapeutics. A major feature of these disorders is impaired insulin action. We have recently developed and validated an exciting new assay for insulin action in fat cells. In this project we propose an exciting research program encompassing major research and biotechnology groups in Australia to u ....Use of a cell based assay to identify novel insulin-sensitising agents. Diabetes and obesity are currently escalating to epidemic proportions in Australia and there is an urgent need to develop new therapeutics. A major feature of these disorders is impaired insulin action. We have recently developed and validated an exciting new assay for insulin action in fat cells. In this project we propose an exciting research program encompassing major research and biotechnology groups in Australia to utilise this technology to identify novel insulin-sensitising agents. These agents will be used for drug discovery purposes by our industry partner ChemGenex and as novel tools to dissect the mechanism of insulin action.Read moreRead less
The role of SGK-1 and SGK-2 in hypertension and nephropathy in diabetes mellitus. The key objective is to define the suitability of the serum glucocorticoid regulated kinases -1 and -2 (SGK-1, -2) as novel drug discovery targets. A specific inhibitor targeting SGK-1 and -2 will be tested to determine if it reverses the enhanced sodium reabsorption and extracellular matrix production characteristic of progressive renal failure in in vitro models models of renal disease. These inhibitors present a ....The role of SGK-1 and SGK-2 in hypertension and nephropathy in diabetes mellitus. The key objective is to define the suitability of the serum glucocorticoid regulated kinases -1 and -2 (SGK-1, -2) as novel drug discovery targets. A specific inhibitor targeting SGK-1 and -2 will be tested to determine if it reverses the enhanced sodium reabsorption and extracellular matrix production characteristic of progressive renal failure in in vitro models models of renal disease. These inhibitors present an opportunity to control hypertension whilst simultaneously limiting fibrosis in the kidney. Renal failure is steadily increasing and is now the single largest health care cost to the community. These studies will provide the proof of concept required to ultimately bring this novel preventative therapy to the community.Read moreRead less
Epidemiological modelling of cardiovascular disease and diabetes in Australia. With Australia's population ageing and becoming increasingly obese, cardiovascular diseases and diabetes are predicted to be a massive burden on our already stretched health system. Preventing the onset of disease is clearly the best management strategy, but we also need effective treatment strategies for those with these diseases, and we need to ensure that we are spending our healthcare dollars in the most effectiv ....Epidemiological modelling of cardiovascular disease and diabetes in Australia. With Australia's population ageing and becoming increasingly obese, cardiovascular diseases and diabetes are predicted to be a massive burden on our already stretched health system. Preventing the onset of disease is clearly the best management strategy, but we also need effective treatment strategies for those with these diseases, and we need to ensure that we are spending our healthcare dollars in the most effective and cost-effective manner to achieve these aims. This research will evaluate how best to do this in a specifically Australian context.Read moreRead less
Development of computer-based decision support tools using population pharmacokinetic/pharmacodynamic models. Diabetes is an epidemic that presents an enormous burden to health systems of both developed and developing nations. Australia spends an estimated $35 billion on the condition annually, with costs set to rise with increasing diagnosis rates. Additionally, the burden of diabetes is more prominent in indigenous Australians. We intend to improve management of this disease in non-indigenous ....Development of computer-based decision support tools using population pharmacokinetic/pharmacodynamic models. Diabetes is an epidemic that presents an enormous burden to health systems of both developed and developing nations. Australia spends an estimated $35 billion on the condition annually, with costs set to rise with increasing diagnosis rates. Additionally, the burden of diabetes is more prominent in indigenous Australians. We intend to improve management of this disease in non-indigenous and indigenous Australians by development of a user-friendly computer-based decision support tool for doctors. Once established, this tool will have applications in other fields of health care where support is needed to make informed dosing decisions for critical medications and have the potential to reduce financial and social impacts of chronic disease.Read moreRead less
Identifying genes that influence clinical course and susceptibility in multiple sclerosis. This project aims to identify the genetic basis of multiple sclerosis (MS), the most common neurologic disease in young Australian adults. MS urgently needs research to identify predisposition, aid early diagnosis and provide bona fide molecular targets for new therapies. This will benefit people with MS and those susceptible to it. Crucial new knowledge identified will benefit other major areas of MS rese ....Identifying genes that influence clinical course and susceptibility in multiple sclerosis. This project aims to identify the genetic basis of multiple sclerosis (MS), the most common neurologic disease in young Australian adults. MS urgently needs research to identify predisposition, aid early diagnosis and provide bona fide molecular targets for new therapies. This will benefit people with MS and those susceptible to it. Crucial new knowledge identified will benefit other major areas of MS research including epidemiology, immunology and neurobiology. Collaboration of 8 major Australian institutions is also important for this project and future studies. The team will have access to a new national MS GeneBank (platform) with samples from 2240 patients that should generate findings important to world-wide MS genetic knowledge.Read moreRead less
Risks to human health and the ecosystem from feral pigs in Perth metropolitan water catchments. This project aims to investigate the potential risk feral pigs pose to public health through the dissemination of water borne pathogens within water catchment areas, and to investigate their role in the maintenance and spread of diseases of public and animal health concern in the south west of Western Australia. As well as providing a frontline approach to protecting our water supplies, this project ....Risks to human health and the ecosystem from feral pigs in Perth metropolitan water catchments. This project aims to investigate the potential risk feral pigs pose to public health through the dissemination of water borne pathogens within water catchment areas, and to investigate their role in the maintenance and spread of diseases of public and animal health concern in the south west of Western Australia. As well as providing a frontline approach to protecting our water supplies, this project will also provide valuable data on the nature and extent of the risk feral pigs pose to biodiversity conservation and the environment generally. The outcomes of this research will provide a scientific basis for the development of prioritised strategies for the control of feral pigs in Western Australia.Read moreRead less