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
The mechanisms and roles of receptor clustering in cell activation and wound healing by growth factors. Growth factors regulate cell proliferation, migration and differentation by interaction with receptors. Such receptors are usually localized at the cell surface, and require intracellular transduction systems to transmit the signal to the cell interior. We have recently shown the hormone-induced clustering of heterologous hormone receptors in cells, and that this occurs with the co-clustering ....The mechanisms and roles of receptor clustering in cell activation and wound healing by growth factors. Growth factors regulate cell proliferation, migration and differentation by interaction with receptors. Such receptors are usually localized at the cell surface, and require intracellular transduction systems to transmit the signal to the cell interior. We have recently shown the hormone-induced clustering of heterologous hormone receptors in cells, and that this occurs with the co-clustering of downstream signalling molecules at sites of engagement with the extracellular matrix. In addition, we have found that cells presented with an extracellular matrix respond better to subsequent growth factor stimulation. The project aims to determine the cellular mechanisms underlying receptor clustering and the basis of the receptor-extracellular matrix interaction. This will enhance our understanding of growth factor function in a number of conditions, including wound healing. We will extend our in vitro results to the animal model to define parameters for enhanced wound repair.Read moreRead less
Establishing evidence for the functional properties of a whole grain in weight management. The successful development of functional foods relies on communicating proven effects. This project aims to prove that the food containing the satiety properties of a whole grain (OG) may help in weight management. We will conduct basic research investigating the link between consumption of OG-containing foods and the regulatory mechanisms of satiety, and test whether the satiety properties can be used to ....Establishing evidence for the functional properties of a whole grain in weight management. The successful development of functional foods relies on communicating proven effects. This project aims to prove that the food containing the satiety properties of a whole grain (OG) may help in weight management. We will conduct basic research investigating the link between consumption of OG-containing foods and the regulatory mechanisms of satiety, and test whether the satiety properties can be used to prevent, reduce and correct body weight gain in the early, middle and late stages of obesity. We will then apply this understanding in a human trial of mildly and long term overweight subjects, to aid the formulation of statements on the potential health benefits from consuming OG.Read moreRead less
Development of natural herbal medicines for managing metabolic syndrome in order to prevent type 2 diabetes. Type 2 diabetes affects almost 7% of Australia~{!/~}s population. Its incidence continues to grow, as indicated by high rates of metabolic syndrome, a pre-stage of type 2 diabetes. Using novel and bio-molecular techniques, we will evaluate the effects and mechanisms of three natural compounds from anti-diabetic Chinese herbs on cellular and rodent models with metabolic syndrome. This stud ....Development of natural herbal medicines for managing metabolic syndrome in order to prevent type 2 diabetes. Type 2 diabetes affects almost 7% of Australia~{!/~}s population. Its incidence continues to grow, as indicated by high rates of metabolic syndrome, a pre-stage of type 2 diabetes. Using novel and bio-molecular techniques, we will evaluate the effects and mechanisms of three natural compounds from anti-diabetic Chinese herbs on cellular and rodent models with metabolic syndrome. This study will provide scientific evidence as to how and why herbal compounds improve insulin resistance and abnormalities in glucose and lipids metabolism. The outcome of this project will support the development of natural products to manage metabolic syndrome and prevent type 2 diabetes.
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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
Differentiation of Cord Blood Stem cells into Thymus (T) cells with regulatory phenotype and function. This project will develop technologies for a stem cell therapy platform based on cord blood stem cells, to enable treatment of autoimmune diseases or transplants. Building on the University of Adelaide's frontier demonstration of differentiation of regulatory Thymus (T) cells from cord blood stem cells, the project will develop techniques to expand the numbers of T cells generated. This has the ....Differentiation of Cord Blood Stem cells into Thymus (T) cells with regulatory phenotype and function. This project will develop technologies for a stem cell therapy platform based on cord blood stem cells, to enable treatment of autoimmune diseases or transplants. Building on the University of Adelaide's frontier demonstration of differentiation of regulatory Thymus (T) cells from cord blood stem cells, the project will develop techniques to expand the numbers of T cells generated. This has the potential to maintain Australia's lead in differentiation of cord blood stem cells and to provide a significant breakthrough in potential treatments of autoimmune diseases (e.g. type 1 diabetes) or transplantation. These diseases affect both a healthy start to life and healthy ageing, and an Australian invention to treat or cure them would have global impact.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
Depression and Diabetes: Prevalence, diagnosis and help-seeking: Influence on depression, glycemic control and quality of life. Depression has been reported to be twice as prevalent and more persistent in individuals with diabetes than in the general population. The current research will investigate the point-prevalence of depression in a large sample of Australian diabetic outpatients using a case-finding instrument (CES-D) and follow-up structured clinical interview where appropriate. Demogr ....Depression and Diabetes: Prevalence, diagnosis and help-seeking: Influence on depression, glycemic control and quality of life. Depression has been reported to be twice as prevalent and more persistent in individuals with diabetes than in the general population. The current research will investigate the point-prevalence of depression in a large sample of Australian diabetic outpatients using a case-finding instrument (CES-D) and follow-up structured clinical interview where appropriate. Demographic, medical, and psychological correlates of depressiono will be investigated. The effects of the screening procedure and diagnosis on help-seeking behaviour, course of the depression, self-care, and glycemic control as well as qualtiy of life will be evaluated after six months.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