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
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
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
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.
Impact of shear stress on vascular adaptations in humans. Large arteries are important for the delivery of blood and oxygen to organs such as the heart and brain. A primary physiological stimulus which controls the size and function of these crucial arteries is the magnitude of flow or, more accurately, shear force that the inner wall of the artery is exposed to. We have developed novel software which enables non-invasive assessment of arterial wall velocity, diameter and blood flow. We will ass ....Impact of shear stress on vascular adaptations in humans. Large arteries are important for the delivery of blood and oxygen to organs such as the heart and brain. A primary physiological stimulus which controls the size and function of these crucial arteries is the magnitude of flow or, more accurately, shear force that the inner wall of the artery is exposed to. We have developed novel software which enables non-invasive assessment of arterial wall velocity, diameter and blood flow. We will assess the impact of acute and chronic changes in wall flow and shear on arterial size and function. We will also develop new software which measures other aspects of artery wall behaviour. These basic human physiology studies have direct implications for assessment of artery health in humans.Read moreRead less
Conserving our native carnivores: the application of molecular genetics to the conservation management of quolls. Quolls, the largest native mammalian predators on mainland Australia, occupy a pivotal ecological niche. All species are declining and are threatened by a variety of interacting environmental processes. This program brings together seven wildlife agencies in a nationwide partnership for understanding and protecting quolls. We will provide new genetic data to test current populatio ....Conserving our native carnivores: the application of molecular genetics to the conservation management of quolls. Quolls, the largest native mammalian predators on mainland Australia, occupy a pivotal ecological niche. All species are declining and are threatened by a variety of interacting environmental processes. This program brings together seven wildlife agencies in a nationwide partnership for understanding and protecting quolls. We will provide new genetic data to test current population and conservation theories using four species of quolls as model taxa to inform us about past histories of populations and to measure parameters of importance to on-ground managers. Results of these projects will help guide management practices for both short- and long-term conservation of these species.Read moreRead less
Inbreeding and Amphibian Decline: from an Individual to a Global Perspective. Amphibian decline is not a phenomenon unique to overseas continents and countries. In the long line of research papers addressing this issue in the best science journals (e.g., Nature and Science), Australian frog decline has even been singled out for specific coverage. This project targets the interplay between habitat fragmentation, loss of genetic variation (inbreeding), and its effects on UV and pathogen resistance ....Inbreeding and Amphibian Decline: from an Individual to a Global Perspective. Amphibian decline is not a phenomenon unique to overseas continents and countries. In the long line of research papers addressing this issue in the best science journals (e.g., Nature and Science), Australian frog decline has even been singled out for specific coverage. This project targets the interplay between habitat fragmentation, loss of genetic variation (inbreeding), and its effects on UV and pathogen resistance in a laboratory model system. It integrates three disciplines (immunobiology, evolutionary genetics, and conservation biology) to resolve fundamental aspects of the drastic, ongoing disappearance of the most significant ecological indicator taxa known today (amphibians). Read moreRead less
Diversity out of a hybrid zone: the interplay of reinforcement and sexual selection in the formation of new species. How are there so many different species? Understanding how new species arise is a fundamental question because it explains current biodiversity and reveals the processes that will continue to give rise to new species in the future. An integral part of any animal species is who they choose to mate with, but how mate choice evolves to create new species remains poorly understood. He ....Diversity out of a hybrid zone: the interplay of reinforcement and sexual selection in the formation of new species. How are there so many different species? Understanding how new species arise is a fundamental question because it explains current biodiversity and reveals the processes that will continue to give rise to new species in the future. An integral part of any animal species is who they choose to mate with, but how mate choice evolves to create new species remains poorly understood. Here I will be studying the processes that affect the evolution of mate choice in an Australian rainforest frog hybrid zone. This system is uniquely suitable for providing internationally important insights into the evolutionary processes that form new species.Read moreRead less
The roles of relatedness and reproductive success in complex social systems of dolphins. Theories of the role of genetic relatedness and reproductive success in mammalian social behaviour have mostly been restricted to primates and carnivores. Coexisting alternative strategies within one population of bottlenose dolphins (Shark Bay WA) offer unprecedented opportunities for such investigations. The male alliances? complexity is unparalleled outside humans, and may require new theory. Some femal ....The roles of relatedness and reproductive success in complex social systems of dolphins. Theories of the role of genetic relatedness and reproductive success in mammalian social behaviour have mostly been restricted to primates and carnivores. Coexisting alternative strategies within one population of bottlenose dolphins (Shark Bay WA) offer unprecedented opportunities for such investigations. The male alliances? complexity is unparalleled outside humans, and may require new theory. Some female lineages show tool-use - rare outside humans, and virtually unknown in marine species. Our behavioural and genetic database has exceptional size, detail and duration for marine mammals, and is most valuable if continued while known individuals' offspring reach a stage where they can be sampled.Read moreRead less