Reducing the fat burden: Identification of novel cellular and molecular targets for alleviating skeletal muscle insulin resistance. Insulin resistance and the associated consequences are a major public health problem in Australia and cost the healthcare system >$1.1 billion/year. Exercise training and thiaziolidinedione (TZD) treatment are therapies that partially ameliorate insulin resistance through distinct and independent mechanisms. However, neither intervention represents a viable long-ter ....Reducing the fat burden: Identification of novel cellular and molecular targets for alleviating skeletal muscle insulin resistance. Insulin resistance and the associated consequences are a major public health problem in Australia and cost the healthcare system >$1.1 billion/year. Exercise training and thiaziolidinedione (TZD) treatment are therapies that partially ameliorate insulin resistance through distinct and independent mechanisms. However, neither intervention represents a viable long-term strategy: exercise training has low compliance, while chronic TZD use is associated with several adverse side effects (edema, weight gain etc.). We will investigate the metabolic, cellular and molecular mechanisms by which these therapies each exert their positive effect on insulin action with the aim of identifying novel targets for future drug interventions. Read moreRead less
Can exercise slow down the epigenetic ageing clock? The aged population accounts for a significant amount of Australia’s health budget. This project aims to uncover novel molecular biomarkers that slow the ageing process and maintain good health for longer. This project aims to use innovative epigenetic analysis to study the molecular ‘clocks’ of young and old populations and to test whether exercise can slow the ageing process. This is expected to lead to a better understanding of how humans re ....Can exercise slow down the epigenetic ageing clock? The aged population accounts for a significant amount of Australia’s health budget. This project aims to uncover novel molecular biomarkers that slow the ageing process and maintain good health for longer. This project aims to use innovative epigenetic analysis to study the molecular ‘clocks’ of young and old populations and to test whether exercise can slow the ageing process. This is expected to lead to a better understanding of how humans respond to changing environments during their lifetime, and will underpin the development of evidence-based personalised health interventions to keep Australians healthier for longer.
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Targeting the genome and epigenome of the exercising skeletal muscle. This project aims is to discover epigenetic and genetic biomarkers that predict fitness changes, following exercise intervention. Individuals are remarkably variable in their responses to exercise interventions, and a large portion of these responses is attributed to genetics, and epigenetics (the effect of the environment on the expression of genes). Using controlled exercise training as a model, this project expects to disco ....Targeting the genome and epigenome of the exercising skeletal muscle. This project aims is to discover epigenetic and genetic biomarkers that predict fitness changes, following exercise intervention. Individuals are remarkably variable in their responses to exercise interventions, and a large portion of these responses is attributed to genetics, and epigenetics (the effect of the environment on the expression of genes). Using controlled exercise training as a model, this project expects to discover epigenetic and genomic markers in skeletal muscle predictive of exercise adaptations. This will contribute to the development and future delivery of targeted and personalised exercise programs for the general population. This has important implications for improving health in the Australian population.Read moreRead less
Molecular networks underlying mitochondrial biogenesis in humans. Mitochondria are essential for life, and we propose a highly-innovative approach (employing multiple, cutting-edge ‘omic’ technologies and bioinformatics) to advance the fundamental understanding of how mitochondria respond and adapt to exercise in humans. The project outcomes should include significant new knowledge and advanced expertise that can be used by others to facilitate additional research outcomes. The project anticipa ....Molecular networks underlying mitochondrial biogenesis in humans. Mitochondria are essential for life, and we propose a highly-innovative approach (employing multiple, cutting-edge ‘omic’ technologies and bioinformatics) to advance the fundamental understanding of how mitochondria respond and adapt to exercise in humans. The project outcomes should include significant new knowledge and advanced expertise that can be used by others to facilitate additional research outcomes. The project anticipates the contribution of innovative tools for molecular biology research, benefiting therapeutic and biotechnology applications. This project will support advanced training of young researchers in frontier technologies, which will expand Australian research capabilities and help produce a higher quality workforce.Read moreRead less
Discovering the role of pH in regulating mitochondrial biogenesis, so as to improve the design of preventative programs aimed at healthy ageing. Mitochondria are essential for life, and maintaining mitochondrial function plays an important role in preventing the progression of many age-related diseases. It has previously been shown that minimising the decrease in muscle pH that occurs during physical activity promotes greater improvements in mitochondrial function. The next step is to discover t ....Discovering the role of pH in regulating mitochondrial biogenesis, so as to improve the design of preventative programs aimed at healthy ageing. Mitochondria are essential for life, and maintaining mitochondrial function plays an important role in preventing the progression of many age-related diseases. It has previously been shown that minimising the decrease in muscle pH that occurs during physical activity promotes greater improvements in mitochondrial function. The next step is to discover the effects of altering pH on acute and chronic activity-induced changes in signalling proteins and genes that are involved in the regulation of skeletal muscle mitochondrial biogenesis. These experiments will significantly advance the knowledge base concerning factors regulating mitochondrial biogenesis, and will contribute to optimising the design of preventative programs aimed at healthy aging.Read moreRead less
Intracellular localisation of insulin signalling proteins in human skeletal muscle following exercise. The metabolic action of insulin in skeletal muscle is enhanced by exercise, but the underlying mechanisms mediating this are unknown. Insulin receptor substrate proteins are key mediators in the intracellular insulin signalling pathway and play a central role in regulating many metabolic events. Our aim is to examine the hypothesis that exercise induces a novel subcellular redistribution of the ....Intracellular localisation of insulin signalling proteins in human skeletal muscle following exercise. The metabolic action of insulin in skeletal muscle is enhanced by exercise, but the underlying mechanisms mediating this are unknown. Insulin receptor substrate proteins are key mediators in the intracellular insulin signalling pathway and play a central role in regulating many metabolic events. Our aim is to examine the hypothesis that exercise induces a novel subcellular redistribution of these insulin receptor substrate proteins in skeletal muscle, such that the metabolic action of insulin is enhanced. Elucidating the mechanisms whereby exercise enhances insulin action underpins the development of new treatments and therapies with the aim of improving skeletal muscle function in health and disease.Read moreRead less
Regulatory mechanisms in skeletal muscle lipid hydrolysis. The regulation of intramuscular triglyceride (fat) utilisation by human skeletal muscle is largely unknown. Our contention is that the specialized protein enzyme, hormone sensitive lipase (HSL), has a fundamental role in intramuscular triacylglycerol utilisation and is regulated by both intramuscular levels of key metabolites and circulating hormone concentrations. We also propose control points subsequent to HSL activation are important ....Regulatory mechanisms in skeletal muscle lipid hydrolysis. The regulation of intramuscular triglyceride (fat) utilisation by human skeletal muscle is largely unknown. Our contention is that the specialized protein enzyme, hormone sensitive lipase (HSL), has a fundamental role in intramuscular triacylglycerol utilisation and is regulated by both intramuscular levels of key metabolites and circulating hormone concentrations. We also propose control points subsequent to HSL activation are important for triglyceride hydrolysis. Our proposed project examines these factors and will enhance our understanding of the regulation of muscle fat use, thereby leading to potential metabolic strategies (nutritional, pharmacological) that enhance skeletal muscle function at rest and during exercise.Read moreRead less
Biological Role of Contraction-Induced Heat Shock Protein Expression. It is well known that mammalian skeletal muscle increases its expression of a group of highly conserved proteins, the heat shock proteins (HSP) in response to repeated contraction. However, the biological role of this expression is unclear. The aim of this project is to determine the biological role of contraction-induced HSP expression. We expect to show that HSP synthesis in response to exercise has three major roles; 1) to ....Biological Role of Contraction-Induced Heat Shock Protein Expression. It is well known that mammalian skeletal muscle increases its expression of a group of highly conserved proteins, the heat shock proteins (HSP) in response to repeated contraction. However, the biological role of this expression is unclear. The aim of this project is to determine the biological role of contraction-induced HSP expression. We expect to show that HSP synthesis in response to exercise has three major roles; 1) to act to repair damaged proteins in recovery from muscle injury 2) to act as a "molecular motor" to translocate proteins from one region of a muscle cell to another and 3) to be released into the circulation in order to act as a central signal to activate immune cells. Such a project will be significant because it will allow for a fundamental understanding as to why these proteins are produced in response to exercise. We expect to enhance our understanding of fundamental cell biology.Read moreRead less