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.
Use of heart rate kinetics during the rest-exercise transition for tracking changes in exercise performance in athletes. The project aims to develop an objective method for assessing fatigue and recovery in athletes during changes in training load. It is intended that this will inform training adjustments to optimise performance and reduce the risk of overtraining and injury. The method assesses the maximal rate of heart rate increase at the start of light exercise (rHRI), and has been shown in ....Use of heart rate kinetics during the rest-exercise transition for tracking changes in exercise performance in athletes. The project aims to develop an objective method for assessing fatigue and recovery in athletes during changes in training load. It is intended that this will inform training adjustments to optimise performance and reduce the risk of overtraining and injury. The method assesses the maximal rate of heart rate increase at the start of light exercise (rHRI), and has been shown in the project team’s early studies to track reductions in exercise performance when an athlete is fatigued from increased training. The project aims to now refine rHRI so it can also track improvements in exercise performance as athletes recover, and to evaluate rHRI in multiple sports and genders. A field test will be developed and mechanisms that allow it to track changes in exercise performance will be investigated.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
Exercise As Medicine For Heart Failure: A Novel Intervention To Improve Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$665,585.00
Summary
Heart failure (HF) is a common, debilitating and expensive disease; prognosis remains poorer than for the most cancers. 30,000 Australians are diagnosed every year and 300,000 live with the HF, at an annual cost of ~$1Billion. Exercise training is effective therapy in HF, because it reverses many of the problems that contribute to the reduced lifespan and impaired quality of life of patients with HF. We will test an exciting new type of exercise that promising greater benefit, at lower risk.
The role of intracellular calcium in fibre-type specific gene expression in skeletal muscle. Muscles contain different fibre types whose composition can be changed by activity. The aim of this proposal is to identify the intracellular mechanisms which control fibre type. Our hypothesis is that different patterns of intracellular calcium determine the pattern of gene expression which determines fibre type. Understanding how gene expression is regulated is a central issue in biology.
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
Intracellular calcium in intact muscle during fatigue and stretch-induced damage. Confocal microscopes can investigate intact tissues during normal function. We will develop and apply this novel approach to muscle. We expect this new approach to become a fundamental new tool for exploring muscle function under near normal conditions. Muscle pain and weakness are common disabilities in humans and we expect this new approach to provide insights into the causes and treatment of these common cond ....Intracellular calcium in intact muscle during fatigue and stretch-induced damage. Confocal microscopes can investigate intact tissues during normal function. We will develop and apply this novel approach to muscle. We expect this new approach to become a fundamental new tool for exploring muscle function under near normal conditions. Muscle pain and weakness are common disabilities in humans and we expect this new approach to provide insights into the causes and treatment of these common conditions.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
Visualising vascular adaptation at the micro-scale in humans. The project aims to investigate fundamental issues in the mechanisms underlying vascular remodelling. It plans to develop novel optical scanning techniques to acquire high-resolution images of the cutaneous microvasculature, alongside absolute blood flow quantification. These novel tools would allow us to visualise and quantify functional and structural adaptations in the microvasculature in response to physiological stimuli such as h ....Visualising vascular adaptation at the micro-scale in humans. The project aims to investigate fundamental issues in the mechanisms underlying vascular remodelling. It plans to develop novel optical scanning techniques to acquire high-resolution images of the cutaneous microvasculature, alongside absolute blood flow quantification. These novel tools would allow us to visualise and quantify functional and structural adaptations in the microvasculature in response to physiological stimuli such as heat exposure and exercise. The non-invasive tool aims to enable us to assess adaptations in microvasculature health, improving our understanding of cardiovascular diseases and type 2 diabetes and potentially reducing the impact of costly and debilitating morbidities such as nephropathy, neuropathy, retinopathy, impotence and skin ulceration.Read moreRead less