Central command neurons integrating cardiorespiratory drive in exercise. The ability to perform exercise is fundamental to human health and welfare. This ability depends upon the co-ordination by the brain of respiratory and cardiovascular function, such that the delivery of oxygen to exercising muscles is maximised. This project will test the idea that there is a specific group of neurons in the brain that drive both the respiratory and cardiovascular changes that occur during exercise, and w ....Central command neurons integrating cardiorespiratory drive in exercise. The ability to perform exercise is fundamental to human health and welfare. This ability depends upon the co-ordination by the brain of respiratory and cardiovascular function, such that the delivery of oxygen to exercising muscles is maximised. This project will test the idea that there is a specific group of neurons in the brain that drive both the respiratory and cardiovascular changes that occur during exercise, and will determine the location and functions of such neurons. Such new knowledge will help us understand how the brain optimises the ability of the body to perform exercise. This is of fundamental importance in sports science, a field in which Australia excels.Read moreRead less
Molecular basis of G protein receptor-effector coupling in epithelial cells. Hundreds of extracellular stimuli act on specific receptors in the plasma membrane of cells resulting in an increase in intracellular calcium which acts as a second messenger to alter cell behaviour. There are, however, many receptors acting through a number of closely related proteins involving tightly regulated interactions which remain poorly understood. This project uses novel techniques to elucidate the molecular b ....Molecular basis of G protein receptor-effector coupling in epithelial cells. Hundreds of extracellular stimuli act on specific receptors in the plasma membrane of cells resulting in an increase in intracellular calcium which acts as a second messenger to alter cell behaviour. There are, however, many receptors acting through a number of closely related proteins involving tightly regulated interactions which remain poorly understood. This project uses novel techniques to elucidate the molecular basis for these interactions by identifying the roles individual proteins play in this complex process.Read moreRead less
Effect of modification of structural and cellular properties of the arterial wall on functional stiffness of large arteries. The Australian population is ageing, becoming more obese and showing earlier onset of age-related conditions such as high blood pressure, heart failure and inflammatory disorders. All these conditions are associated with possible increase arterial stiffness. Inflammatory disorders in Australia affect one in six people, increasing to one in five in the next decade. An equa ....Effect of modification of structural and cellular properties of the arterial wall on functional stiffness of large arteries. The Australian population is ageing, becoming more obese and showing earlier onset of age-related conditions such as high blood pressure, heart failure and inflammatory disorders. All these conditions are associated with possible increase arterial stiffness. Inflammatory disorders in Australia affect one in six people, increasing to one in five in the next decade. An equal proportion is affected by cardiovascular disease. This combined effect poses a massive burden on the national health budget. This project aims to investigate basic mechanism leading to degeneration of function of larger arteries and therapies to reverse the process and reduce cardiovascular risk in the community.Read moreRead less
Computational Reconstruction of Cardiac Pacemaker Activation and Atrial Propagation. This study seeks to develop accurate computer models of electrical activity in pacemaker and atrial cells of the heart, in order to understand how the heartbeat originates and propagates across the atria during normal and abnormal rhythms. In Australia, atrial fibrillation represents the most common form of chronic cardiac arrhythmia encountered in clinical practice, as well as being a major risk factor in strok ....Computational Reconstruction of Cardiac Pacemaker Activation and Atrial Propagation. This study seeks to develop accurate computer models of electrical activity in pacemaker and atrial cells of the heart, in order to understand how the heartbeat originates and propagates across the atria during normal and abnormal rhythms. In Australia, atrial fibrillation represents the most common form of chronic cardiac arrhythmia encountered in clinical practice, as well as being a major risk factor in stroke. Accurate computer modelling of normal and abnormal heart rhythms will provide greater insights into the development of antiarrythmic drugs as well as advancing knowledge of key electrical phenomena in the heart.Read moreRead less
Cellular response to pro-oxidative myoglobin. The heart is vulnerable to oxidative damage as specialised muscle cells termed myocytes are unable to regenerate. Oxidative damage to myocytes decreases cell viability and in turn heart muscle function. Pro-oxidative forms of the protein myoglobin are present in the heart and may play a role in damaging myocytes. This study will determine whether a series of novel synthetic antioxidants inhibit myoglobin-mediated damage to heart muscle and preserve f ....Cellular response to pro-oxidative myoglobin. The heart is vulnerable to oxidative damage as specialised muscle cells termed myocytes are unable to regenerate. Oxidative damage to myocytes decreases cell viability and in turn heart muscle function. Pro-oxidative forms of the protein myoglobin are present in the heart and may play a role in damaging myocytes. This study will determine whether a series of novel synthetic antioxidants inhibit myoglobin-mediated damage to heart muscle and preserve function. This may lead to new therapies to combat cardiovascular disease and enable ageing Australians to maintain productive and independent lifestyles.Read moreRead less
Genetic mechanisms of metabolic control and thermal sensing during thermoregulation. This research will significantly advance understanding of how animals can respond to climate change, and the results will benefit wildlife management processes. The proposed research will lead to collaboration with Prof. Ken Storey an ISI highly cited author and expert in microarray analysis. The cDNA microarray for Crocodylus porosus which I will construct in the proposed research will be a valuable resource ....Genetic mechanisms of metabolic control and thermal sensing during thermoregulation. This research will significantly advance understanding of how animals can respond to climate change, and the results will benefit wildlife management processes. The proposed research will lead to collaboration with Prof. Ken Storey an ISI highly cited author and expert in microarray analysis. The cDNA microarray for Crocodylus porosus which I will construct in the proposed research will be a valuable resource for Australia by increasing collaborations, and it will help find the cause of problems prevalent in the crocodile industry such as runt animals that significantly decrease production efficiency.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.
The role of intracellular calcium stores in cardiac pacemaking. The spontaneous firing of pacemaker cells is central to regulation of the cardiovascular system particularly during exercise. The discovery that pacemaker cell function is modulated in part by calcium ions will change our understanding of the changes in heart rate during exercise and in diseases which affect the pacemaker cells. Better understanding of the way in which spontaneous activity of these cells is regulated is the key to ....The role of intracellular calcium stores in cardiac pacemaking. The spontaneous firing of pacemaker cells is central to regulation of the cardiovascular system particularly during exercise. The discovery that pacemaker cell function is modulated in part by calcium ions will change our understanding of the changes in heart rate during exercise and in diseases which affect the pacemaker cells. Better understanding of the way in which spontaneous activity of these cells is regulated is the key to controlling or modifying their function.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
Biochemical properties of S-nitroso-myoglobin and its role in regulating nitric oxide bio-availability. Nitric oxide (NO) stimulates blood vessel dilation. Vessel dilation is essential to maintaining blood pressure. Altered NO-regulation leads to vessel dysfunction. Within blood vessels, myoglobin regulates NO concentrations through oxidation and binding reactions. In contrast, S-nitroso-myoglobin represents a novel source of NO in humans. The goal of this study is to expand the knowledge on ....Biochemical properties of S-nitroso-myoglobin and its role in regulating nitric oxide bio-availability. Nitric oxide (NO) stimulates blood vessel dilation. Vessel dilation is essential to maintaining blood pressure. Altered NO-regulation leads to vessel dysfunction. Within blood vessels, myoglobin regulates NO concentrations through oxidation and binding reactions. In contrast, S-nitroso-myoglobin represents a novel source of NO in humans. The goal of this study is to expand the knowledge on NO-regulation by myoglobin through determining S-nitroso-myoglobin's - chemical stability, rates of formation and decay, concentration in human vessels and whether it can cause blood vessel dilation similar to authentic NO. Such novel data represents a major fundamental advance in understanding the role of myoglobin in NO-homeostasis.Read moreRead less