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
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
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
Electrochemical Applications of Plastic Crystalline Electrolytes. A number of new and emerging electrochemical device applications such as lithium batteries, dye-sensitized solar cells, electrochemical capacitors, actuators and bio-sensors are limited by their need for a liquid electrolyte. Many of these devices are considered vital to energy efficiency and the lowering of greenhouse gas emissions. The recent discovery of ambient temperature plastic crystalline electrolyte materials by the Monas ....Electrochemical Applications of Plastic Crystalline Electrolytes. A number of new and emerging electrochemical device applications such as lithium batteries, dye-sensitized solar cells, electrochemical capacitors, actuators and bio-sensors are limited by their need for a liquid electrolyte. Many of these devices are considered vital to energy efficiency and the lowering of greenhouse gas emissions. The recent discovery of ambient temperature plastic crystalline electrolyte materials by the Monash Electrolytes group has raised the possibility of solving this problem. In this project new plastic crystalline electrolyte materials will be developed to suit these applications and their electrochemical properties investigated. Laboratory prototype devices will be prepared and tested and via collaborations with appropriate device developers, their performance evaluted.Read moreRead less
Erosion Morphodynamics and Evolution of Shore Platforms. Rocky coasts consist of a cliff and often a platform at the base which protects the cliff from wave energy. Such coasts undergo continuous erosion that may threaten property. Climate change may worsen this situation. Despite the importance of platforms in coastal management they remain poorly studied. This project seeks to improve scientific knowledge and understanding of the development and erosion of shore platforms, the relationships ....Erosion Morphodynamics and Evolution of Shore Platforms. Rocky coasts consist of a cliff and often a platform at the base which protects the cliff from wave energy. Such coasts undergo continuous erosion that may threaten property. Climate change may worsen this situation. Despite the importance of platforms in coastal management they remain poorly studied. This project seeks to improve scientific knowledge and understanding of the development and erosion of shore platforms, the relationships between shore platform and cliff retreat and the processes that drive erosion. As a result we will understand how rock coasts with platforms develop and change, especially as sea levels change and be better able to manage the coast in response to climate change. 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
Membrane-associated structure and the effect of metals on Abeta peptide from Alzheimer's disease. Alzheimer's disease currently affects 5% of Australians over 65, and will triple by year 2050 without an effective therapy. Much research to understand the causes of the disease has focused on the distinctive amyloid deposits found in patients' cerebral tissue. Recent evidence suggests that nerve cell death is actually directly caused by soluble forms of the protein fragments and metals that form th ....Membrane-associated structure and the effect of metals on Abeta peptide from Alzheimer's disease. Alzheimer's disease currently affects 5% of Australians over 65, and will triple by year 2050 without an effective therapy. Much research to understand the causes of the disease has focused on the distinctive amyloid deposits found in patients' cerebral tissue. Recent evidence suggests that nerve cell death is actually directly caused by soluble forms of the protein fragments and metals that form these deposits. We will investigate the specific molecular structure of these fragments with metals in relation to vesicles which mimic the nerve cell surface. This information may facilitate future biomedical efforts work to develop therapies, as well as develop general techniques to study similar structural problems.Read moreRead less
Smart Materials Between Two and Three Dimensions. Shape-memory alloys involving martensitic transformations, are important as smart materials. Both the transformation nucleation and the sample morphology are unsolved issues relevant for these applications. Of particular note are the softening of certain lattice-vibrational frequencies, the development of a tweed-like microstructure on cooling the material and the role of defects, particularly the sample surface, in the transformation process. ....Smart Materials Between Two and Three Dimensions. Shape-memory alloys involving martensitic transformations, are important as smart materials. Both the transformation nucleation and the sample morphology are unsolved issues relevant for these applications. Of particular note are the softening of certain lattice-vibrational frequencies, the development of a tweed-like microstructure on cooling the material and the role of defects, particularly the sample surface, in the transformation process. This project addresses these issues using model materials in thin-film and bulk-crystal forms. Capacitance dilatometry, optical, electron and scanning-probe microscopies, and x-ray techniques, will unlock an understanding of the physical and metallurgical conditions controlling these transformations.Read moreRead less
Interfacial Nanofluids. The fundamental understanding of Colloid and Surface Chemistry will be significantly enhanced through the understanding of the formation and properties of interfacial nanofluids. In addition, this project will provide the knowledge of the influence of nanofluids on the lubrication and the surface interaction. The future results will likely have great impact on the development of miniature devices, lab-on-a-chip and microfludics or nanofluidics systems, water treatment, m ....Interfacial Nanofluids. The fundamental understanding of Colloid and Surface Chemistry will be significantly enhanced through the understanding of the formation and properties of interfacial nanofluids. In addition, this project will provide the knowledge of the influence of nanofluids on the lubrication and the surface interaction. The future results will likely have great impact on the development of miniature devices, lab-on-a-chip and microfludics or nanofluidics systems, water treatment, minerals processing, the food industries, pumping of fuel and water, and other processes. And the research described in this proposal will help to maintain the high international profile of Australian science in the field of Colloid and Surface Research. Read moreRead less