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
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
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668440
Funder
Australian Research Council
Funding Amount
$850,000.00
Summary
Advanced technology for transcriptomics, genomics and gene mapping. Acquistion of the equipment requested in this application will maintain the expertise developed by researchers within New South Wales and attract and retain exceptional individuals who can contribute to our understanding of how genes interact with one another. The benefit of such an enhances facility will be the delivery of a better functional understanding of health and disease which will provide both community and national be ....Advanced technology for transcriptomics, genomics and gene mapping. Acquistion of the equipment requested in this application will maintain the expertise developed by researchers within New South Wales and attract and retain exceptional individuals who can contribute to our understanding of how genes interact with one another. The benefit of such an enhances facility will be the delivery of a better functional understanding of health and disease which will provide both community and national benefits. The primary purpose of this LIEF application is to standardize approaches to the study of genome function across the nodes of the Ramaciotti facility and to expand the capacities of the facility to cope with the increased demand in this technology. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560714
Funder
Australian Research Council
Funding Amount
$509,131.00
Summary
Phenotype genotype comparisons using functional genomic approaches. The Ramaciotti Centre for Gene Function Analysis comprises a multi-node network across the state of NSW involving 4 major universities. Using the resources of the Centre, over 100 researchers are undertaking projects comparing genotypes and phenotypes utilising state-of-art genomic based strategies comprising microarrays and SNP analysis. This application will further expand the resources available to researchers with the additi ....Phenotype genotype comparisons using functional genomic approaches. The Ramaciotti Centre for Gene Function Analysis comprises a multi-node network across the state of NSW involving 4 major universities. Using the resources of the Centre, over 100 researchers are undertaking projects comparing genotypes and phenotypes utilising state-of-art genomic based strategies comprising microarrays and SNP analysis. This application will further expand the resources available to researchers with the addition of: (1) Affymetrix based chip microarrays; (2) Options for setting up SNP analysis for both high throughput, and medium throughput analyses and (3) Expanding the robotics options available throught the Centre.Read moreRead less
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
Regulation of nuclear localisation of the AreA transcription factor in Aspergillus nidulans. An understanding of the means by which the expression of genes is regulated is of fundamental significance. Changes in gene expression are central to the development, growth and viability of all cells and their response to environmental changes/stresses. This study uses the fungus Aspergillus nidulans as an excellent molecular genetic tool to investigate how a key regulatory protein controls gene expres ....Regulation of nuclear localisation of the AreA transcription factor in Aspergillus nidulans. An understanding of the means by which the expression of genes is regulated is of fundamental significance. Changes in gene expression are central to the development, growth and viability of all cells and their response to environmental changes/stresses. This study uses the fungus Aspergillus nidulans as an excellent molecular genetic tool to investigate how a key regulatory protein controls gene expression in response to nitrogen starvation stress. Our understanding of these dynamic processes informs our approaches to the development of cancer therapies, to commercial biotechnology application and to control of human, plant and animal pathogens in which the infectious process is triggered by environmental stress. Read moreRead less
Evolution of host relationships among the parasitic wasps inferred from morphology, DNA sequences and mitochondrial genome organisation. The parasitic Hymenoptera (wasps) are extensively used as biological control agents of agricultural and horticultural pests worldwide, but detailed information on their evolutionary relationships, how they have coevolved with major host groups, and the patterns of host relationships across various wasp families are lacking. This project will employ DNA sequence ....Evolution of host relationships among the parasitic wasps inferred from morphology, DNA sequences and mitochondrial genome organisation. The parasitic Hymenoptera (wasps) are extensively used as biological control agents of agricultural and horticultural pests worldwide, but detailed information on their evolutionary relationships, how they have coevolved with major host groups, and the patterns of host relationships across various wasp families are lacking. This project will employ DNA sequence data from 'new' genes, information on mitochondrial genome organisation, as well as morphology, to generate robust phylogenies for braconid and scelionid wasps that can be used to determine patterns of host utilisation and predict hosts for wasp groups where this information is currently unknown.Read moreRead less