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
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.
Electrophysiological and Anatomical Characterization of the Coronary Sinus Musculature and its Relationship to the Atria. This series of experiments will characterise the normal coronary sinus musculature and its connectivity to the atria of the heart and establish their electrical relationships. The underlying characteristics of the muscular connections will also be evaluated with a view to possible future manipulations of the system. Understanding normal heart impulse propagation is paramount ....Electrophysiological and Anatomical Characterization of the Coronary Sinus Musculature and its Relationship to the Atria. This series of experiments will characterise the normal coronary sinus musculature and its connectivity to the atria of the heart and establish their electrical relationships. The underlying characteristics of the muscular connections will also be evaluated with a view to possible future manipulations of the system. Understanding normal heart impulse propagation is paramount before we can understand and develop treatments for dealing with heart problems. This information will facilitate the development of techniques to treat and prevent heart rhythm disorders that are a common cause of morbidity in the community.Read moreRead less
Do depolarizing currents in the endothelium evoke contraction of vascular smooth muscle? Establishment of our concept involving a novel constricting influence in blood vessels will have two major benefits. First, it will keep Australian research at the leading edge in blood vessel research and thus maintain a very high international profile for Australian science. Second, our concept represents a whole new field of therapeutic potential for treating a range of vascular diseases involving excess ....Do depolarizing currents in the endothelium evoke contraction of vascular smooth muscle? Establishment of our concept involving a novel constricting influence in blood vessels will have two major benefits. First, it will keep Australian research at the leading edge in blood vessel research and thus maintain a very high international profile for Australian science. Second, our concept represents a whole new field of therapeutic potential for treating a range of vascular diseases involving excessive constriction of blood vessels. The development and manufacture of drugs in Australia would contribute to the national economy, and their consumption could improve the quality of life for those suffering from vascular diseases amenable to treatment by such drugs, likely to include pre-eclampsia, diabetes, hypertension.
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The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and ....The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and damaged proteins. This work is important because some diseases (eg, Alzheimers disease) involve the toxic effects of abnormal protein precipitation. Understanding how clusterin works may help in developing better treatments for these diseases.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
Environmental Control of Developmental Plasticity of Vertebrate Cardio-Pulmonary Systems. Our research will generate the first comprehensive picture of how environmental conditions are transduced to control the development of the vertebrate respiratory and cardiovascular systems over the perinatal period. The research will demonstrate how physiological systems are modified and hence evolve. Moreover, understanding the developmental pathology in embryos induced by changing environmental condition ....Environmental Control of Developmental Plasticity of Vertebrate Cardio-Pulmonary Systems. Our research will generate the first comprehensive picture of how environmental conditions are transduced to control the development of the vertebrate respiratory and cardiovascular systems over the perinatal period. The research will demonstrate how physiological systems are modified and hence evolve. Moreover, understanding the developmental pathology in embryos induced by changing environmental conditions (especially exposure to steroid-like pollutants) is crucial to support breeding programs of endangered species and may improve veterinary and medicinal treatment of premature animals and humans. This multi-disciplinary, international collaboration provides an international training ground and two-way exchange of students and postdocs.Read moreRead less
Coping With Pressure: Respiratory Biology of Marine Mammals. Many marine mammals undergo severe, protracted lung collapse during deep dives. They also exhibit prolonged periods of apnea during sleep. In humans, lung collapse and sleep apnea both represent severe respiratory dysfunction. Pulmonary surfactant, a complex mixture that lines the lung, stabilises the lungs in terrestrial mammals, preventing lung collapse. Here, we propose a comprehensive examination of respiratory function in marine m ....Coping With Pressure: Respiratory Biology of Marine Mammals. Many marine mammals undergo severe, protracted lung collapse during deep dives. They also exhibit prolonged periods of apnea during sleep. In humans, lung collapse and sleep apnea both represent severe respiratory dysfunction. Pulmonary surfactant, a complex mixture that lines the lung, stabilises the lungs in terrestrial mammals, preventing lung collapse. Here, we propose a comprehensive examination of respiratory function in marine mammals. This study will significantly advance our knowledge of the diving physiology of Australian marine mammals. A detailed examination of the respiratory and surfactant systems of marine mammals may also reveal adaptations that enable these animals to endure sleep apnea and lung collapse.Read moreRead less
Optimised distributed stimulation of muscle. The project aims to extend to humans, a method of producing a non-fatiguing, smooth, submaximal muscle contraction. The method using multiple electrodes, stimulated at different times, with those times being adjusted for optimum smoothness at low stimulation rates. This will enable the gathering of information about the mechanics of muscle undergoing near physiological contractions, which will be of interest to researchers in Biomechanics. It will ....Optimised distributed stimulation of muscle. The project aims to extend to humans, a method of producing a non-fatiguing, smooth, submaximal muscle contraction. The method using multiple electrodes, stimulated at different times, with those times being adjusted for optimum smoothness at low stimulation rates. This will enable the gathering of information about the mechanics of muscle undergoing near physiological contractions, which will be of interest to researchers in Biomechanics. It will also be a step towards the restoration of function to spinal cord injured patients.Read moreRead less
Relaxin: molecular mechanisms of action in the reversal of fibrosis. Defects in relaxin and relaxin receptors are increasingly implicated as a cause of fibrosis which is associated with many disease processes. This study will examine the molecular mechanisms linking relaxin and fibrosis and will determine whether relaxin can be used to reverse the condition.