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
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
Discovery Early Career Researcher Award - Grant ID: DE140100864
Funder
Australian Research Council
Funding Amount
$394,334.00
Summary
Discovering The Effect of alpha-actinin-3 Deficiency on Muscle Adaptations to Exercise Training in Humans. The protein alpha-actinin-3 is expressed in fast muscle fibres. A common gene variant results in complete deficiency in alpha-actinin-3 that has been shown to influence athletic performance. A mouse model has been previously generated to demonstrate that alpha-actinin-3 deficiency results in a significant shift in fast muscle fibres, towards the slow, more efficient muscle fibres. This proj ....Discovering The Effect of alpha-actinin-3 Deficiency on Muscle Adaptations to Exercise Training in Humans. The protein alpha-actinin-3 is expressed in fast muscle fibres. A common gene variant results in complete deficiency in alpha-actinin-3 that has been shown to influence athletic performance. A mouse model has been previously generated to demonstrate that alpha-actinin-3 deficiency results in a significant shift in fast muscle fibres, towards the slow, more efficient muscle fibres. This project will demonstrate the effects of alpha-actinin-3 deficiency on the characteristics of human muscle pre and post exercise training. Outcomes will include major applications for personalising health recommendations and in designing preventative programs for ageing.Read moreRead less
Regulated muscle-based thermogenesis for body temperature regulation. Mammals maintain a constant core body temperature by generating heat in resting muscles in response to changes in the environmental temperatures. This project aims to show how the skeletal muscles that are closer to the body core contribute the majority of heat, how the muscles of the limbs have their heat generation curtailed as necessary, and how this is coordinated by the body in response to ambient temperature. Project out ....Regulated muscle-based thermogenesis for body temperature regulation. Mammals maintain a constant core body temperature by generating heat in resting muscles in response to changes in the environmental temperatures. This project aims to show how the skeletal muscles that are closer to the body core contribute the majority of heat, how the muscles of the limbs have their heat generation curtailed as necessary, and how this is coordinated by the body in response to ambient temperature. Project outcomes include defining, for the first time, how heat generation in the muscles of the body is regulated. This should provide critical knowledge of mammalian evolution and ways to manipulate metabolism, which may provide ways to assist the production of meat by managing hypothermia and hyperthermia risk in agriculture.Read moreRead less
Regulation Of Protein Kinases And Their Substrates
Funder
National Health and Medical Research Council
Funding Amount
$553,197.00
Summary
Our research is concerned with the control of the body's energy metabolism via an enzyme called AMPK. This enzyme is at the hub of metabolic control in response to diet and exercise. AMPK controls energy expenditure in response to demand as well as appetite. It is well recognized that diet and sedentary life-styles are major contributors to obesity and cardiovascular disease. We are testing how a new drug activates AMPKand how energy expenditure can be increased.
Organisation and function of embedded oil glands in eucalypts. Some eucalypt leaves contain large quantities of essential oils, which have been extracted for commercial purposes for many years. Advancement of this industry, however, requires basic research directed at enhancing both the yield of oil and the range of valuable constituents. This project will make use of a new protocol for isolating and purifying the foliar oil-producing glands to identify a new suite of oil gland constituents and ....Organisation and function of embedded oil glands in eucalypts. Some eucalypt leaves contain large quantities of essential oils, which have been extracted for commercial purposes for many years. Advancement of this industry, however, requires basic research directed at enhancing both the yield of oil and the range of valuable constituents. This project will make use of a new protocol for isolating and purifying the foliar oil-producing glands to identify a new suite of oil gland constituents and to understand the way in which they are made and deployed in the gland. The research will also contribute to our general understanding of oil gland structure and function.Read moreRead less
Protein Complexes and Supercomplexes of Plant Organelles. Ample parts of plant primary metabolism occur in subcellular structures called mitochondria, plastids and peroxisomes. They are vital for plant growth and development and are central to the early success of germinating and growing seedlings. This project intends to analyze the protein complexes and supercomplexes within these organelles using state of the art instrumentation and technologies. Findings from this research have the potential ....Protein Complexes and Supercomplexes of Plant Organelles. Ample parts of plant primary metabolism occur in subcellular structures called mitochondria, plastids and peroxisomes. They are vital for plant growth and development and are central to the early success of germinating and growing seedlings. This project intends to analyze the protein complexes and supercomplexes within these organelles using state of the art instrumentation and technologies. Findings from this research have the potential to directly flow into the plant biotechnology industry and could assist the future development of Australian agriculture through genetic improvements. The expertise developed by this work will ensure that Australia is well placed to meet future needs and to generally improve agricultural technology. Read moreRead less