Improving determinants of Australian sports talent identification and development: a multi-disciplinary approach. Sport is important to many Australians. Our sport successes enhance our national identity, generate community pride and attract mega sport events. Currently our sport talent identification and development (TID) systems have been surpassed by our international rivals who borrowed from and improved our knowledge. This project will help regain Australia's international advantage and aga ....Improving determinants of Australian sports talent identification and development: a multi-disciplinary approach. Sport is important to many Australians. Our sport successes enhance our national identity, generate community pride and attract mega sport events. Currently our sport talent identification and development (TID) systems have been surpassed by our international rivals who borrowed from and improved our knowledge. This project will help regain Australia's international advantage and again make Australian TID the international benchmark. Results will highlight the role of TID practices in improving recreational participation and maximising, attracting, developing and retaining sport talent. This will result in improved use of sports limited TID funding by providing greater understanding of factors that influence elite selection and sport development.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
Discovering And Targeting Genes Regulating Skeletal Muscle Function, Metabolism, And Adaptations To Exercise Interventions
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Muscle wasting and decreased in mitochondrial function due to ageing or lack of physical activity are associated with reduced quality of life. The overarching aim is to develop a unique research program focusing on targeting specific genes, and to discover novel genes regulating muscle wasting and mitochondrial (dis)function. I anticipate this approach to assist in the development of targeted and personalised prevention and therapy for diseases associated with muscle (dis)function.
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
Optimising Exercise and Nutrition Throughout the Life Cycle. During the past decade the proportion of Australia's population aged 65 years and over has increased to 13% (2.7 million). During the same period, the proportion of the population aged 85 years and over has more than doubled and is now the fastest growing subpopulation in Australia. As the number of elderly persons continues to grow, sarcopenia-related conditions will have a dramatic and inevitable impact on the lives of all Australian ....Optimising Exercise and Nutrition Throughout the Life Cycle. During the past decade the proportion of Australia's population aged 65 years and over has increased to 13% (2.7 million). During the same period, the proportion of the population aged 85 years and over has more than doubled and is now the fastest growing subpopulation in Australia. As the number of elderly persons continues to grow, sarcopenia-related conditions will have a dramatic and inevitable impact on the lives of all Australians. The novel dietary protocols developed from the results of the studies undertaken in this proposal will translate into better treatment options for reversing age-dependent muscle degeneration. This is a critical first step for improving the standard of living for a large portion of Australian society.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
Effectiveness of Intervention Strategies to Promote Physical Activity Among Insufficiently Active Adults. This project will determine the cost-effectiveness of 2 types of physical activity (PA) interventions based around the workplace. 480 participants will be randomly assigned to PA intervention groups or controls. Interventions are either a (1) self-regulated, pedometer-based program or a (2) semi-structured, 40-day initiation to more moderately-vigorous PA. Both are designed to increase self- ....Effectiveness of Intervention Strategies to Promote Physical Activity Among Insufficiently Active Adults. This project will determine the cost-effectiveness of 2 types of physical activity (PA) interventions based around the workplace. 480 participants will be randomly assigned to PA intervention groups or controls. Interventions are either a (1) self-regulated, pedometer-based program or a (2) semi-structured, 40-day initiation to more moderately-vigorous PA. Both are designed to increase self-efficacy and impact on positive PA behaviours. Long-term, behavioural change and job-related outcomes will be evaluated by following participants for 12 months after the interventions.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