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
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
The Immunoregulatory Role of the Endogenous Cannabinoid Anandamide. Anandamides are naturally occurring fatty acids that act at the cannabinoid receptor expressed in the brain and periphery. A new proposal by our research group challenges traditional models of the disease process by suggesting that the anandamide system is an important imunoregulatory system that can be targeted by invading pathogens. We propose that disruption to the anandamide system, by bacteria or viruses acting at the rece ....The Immunoregulatory Role of the Endogenous Cannabinoid Anandamide. Anandamides are naturally occurring fatty acids that act at the cannabinoid receptor expressed in the brain and periphery. A new proposal by our research group challenges traditional models of the disease process by suggesting that the anandamide system is an important imunoregulatory system that can be targeted by invading pathogens. We propose that disruption to the anandamide system, by bacteria or viruses acting at the receptor to block immunological responses, contributes to chronic illness states. At this point we have good evidence that anandamides are immunoregulators, however, we have very little knowledge of their precise physiological role. The aim of this research is to begin to characterise the immunoregulatory role of the anandamide system. This project will provide a comprehensive understanding of this endogenous control system, the immunological properties of which have not previously been described. The outcome of this research may lead to the identification of new avenues for the development of pharmaceutical interventions that can target this system.Read moreRead less
Plasticity in placental vasculature and the evolution of viviparity in lizards. This cross-disciplinary research will provide thorough understanding of the reproductive physiology of animals with different forms of reproduction, information critical for conservation and management of Australia's biodiversity. Australia's unique reptiles provide the best animal system in the world for research in this area. Our research on maternal-embryonic interactions in this animal model has direct implicatio ....Plasticity in placental vasculature and the evolution of viviparity in lizards. This cross-disciplinary research will provide thorough understanding of the reproductive physiology of animals with different forms of reproduction, information critical for conservation and management of Australia's biodiversity. Australia's unique reptiles provide the best animal system in the world for research in this area. Our research on maternal-embryonic interactions in this animal model has direct implications for understanding some medical disorders, such as human angiogenic disorders. The research will strengthen ties internationally through research in South Africa, and provide training in combined biological and medical technologies. It will maintain Australia's long-term leadership in this area of research.Read moreRead less
Responses of reptiles to fluctuating thermal environments: behaviour or biochemistry? I propose a conceptual shift in the way thermal physiology of reptiles is interpreted, questioning the predominant role of behaviour in reptilian thermoregulation. I will test the hypothesis that changes in cellular biochemistry are an important mechanism by which reptiles respond to environmental fluctuations. I will determine the relationship between metabolic enzyme activity and performance functions, and ....Responses of reptiles to fluctuating thermal environments: behaviour or biochemistry? I propose a conceptual shift in the way thermal physiology of reptiles is interpreted, questioning the predominant role of behaviour in reptilian thermoregulation. I will test the hypothesis that changes in cellular biochemistry are an important mechanism by which reptiles respond to environmental fluctuations. I will determine the relationship between metabolic enzyme activity and performance functions, and the results may call for a re-assessment of current concepts such as the notion that reptiles must achieve "preferred" body temperatures to maintain performance.Read moreRead less
Anandamide activated chloride channels in sensory neurons. We are seeking to understand how the nerve cells that sense our environment are regulated by signalling molecules produced by our body. Understanding how these cells function in normal conditions is essential as basis for understanding how they may function abnormally in physically stressful situations or in chronic pain conditions. The work may eventually lead to better treatments for a wide range of disorders that involve the sensory ....Anandamide activated chloride channels in sensory neurons. We are seeking to understand how the nerve cells that sense our environment are regulated by signalling molecules produced by our body. Understanding how these cells function in normal conditions is essential as basis for understanding how they may function abnormally in physically stressful situations or in chronic pain conditions. The work may eventually lead to better treatments for a wide range of disorders that involve the sensory nervous system. Read moreRead less