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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Novel sources of nitric oxide (NO) in cells: Implications for an endocrine role for NO. Communication between cells is essential for coordinating and controlling a healthy body. A key regulator and cell-communicating molecule is the gas, nitric oxide. Although nitric oxide is a simple substance we still do not fully understand all aspects of its cellular functions. It is assumed that nitric oxide is synthesised in the body and, after release, is rapidly metabolized and eliminated. Reductions in ....Novel sources of nitric oxide (NO) in cells: Implications for an endocrine role for NO. Communication between cells is essential for coordinating and controlling a healthy body. A key regulator and cell-communicating molecule is the gas, nitric oxide. Although nitric oxide is a simple substance we still do not fully understand all aspects of its cellular functions. It is assumed that nitric oxide is synthesised in the body and, after release, is rapidly metabolized and eliminated. Reductions in the levels of nitric oxide in the body are associated with several diseases states and states of dysfunction including cardiovascular disease, diabetes and also impotence. Professor Triggle's study seeks to characterize how tissues may store nitric oxide, thus prolonging the life of nitric oxide, and how such stores are released. Read moreRead less
Mechanisms of calcium handling and their role in controlling smooth muscle function: evidence from transgenic mice. Calcium movements into and out of the cytoplasm of smooth muscle cells are regulated primarily by a variety of proteins located in the plasma membrane and in the sarcoplasmic reticulum and play a central role in controlling the contractile state of smooth muscle. Understanding the mechanisms that control intracellular calcium levels is fundamental to understanding smooth muscle fu ....Mechanisms of calcium handling and their role in controlling smooth muscle function: evidence from transgenic mice. Calcium movements into and out of the cytoplasm of smooth muscle cells are regulated primarily by a variety of proteins located in the plasma membrane and in the sarcoplasmic reticulum and play a central role in controlling the contractile state of smooth muscle. Understanding the mechanisms that control intracellular calcium levels is fundamental to understanding smooth muscle function. This project will employ a unique approach, involving the use of mice with targeted disruptions to genes encoding key calcium transport proteins, to gain new knowledge on the contribution of various calcium handling pathways to overall control of smooth muscle function.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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453630
Funder
Australian Research Council
Funding Amount
$274,692.00
Summary
High-Speed Confocal Microscope Live Cell Recording System. The high-speed confocal microscope live cell recording system we are establishing represents new generation equipment. It allows quality imaging of selected subcellular regions of live cells combined with simultaneous electrophysiological recording at rates and sensitivity hitherto not possible. This equipment provides a window of opportunity for major research advances in that it allows real-time two and three-dimensional imaging of fun ....High-Speed Confocal Microscope Live Cell Recording System. The high-speed confocal microscope live cell recording system we are establishing represents new generation equipment. It allows quality imaging of selected subcellular regions of live cells combined with simultaneous electrophysiological recording at rates and sensitivity hitherto not possible. This equipment provides a window of opportunity for major research advances in that it allows real-time two and three-dimensional imaging of fundamental cellular activities that previously could not be viewed. It will allow major advances in priority health-related research and will provide an ideal research tool to introduce young scientists and students to cutting edge research.Read moreRead less
Regulation of large artery stiffness by endothelium-derived mediators and effects on the arterial pressure waveform. Stiffening of arteries is an important cardiovascular risk factor and increases with age, high blood pressure, high cholesterol and diabetes. Cells that line the blood vessels (endothelial cells), become damaged and this reduces the available amount of a dilator substance, nitric oxide, and increases the activity of a constrictor substance, endothelin-1. We have shown that nitric ....Regulation of large artery stiffness by endothelium-derived mediators and effects on the arterial pressure waveform. Stiffening of arteries is an important cardiovascular risk factor and increases with age, high blood pressure, high cholesterol and diabetes. Cells that line the blood vessels (endothelial cells), become damaged and this reduces the available amount of a dilator substance, nitric oxide, and increases the activity of a constrictor substance, endothelin-1. We have shown that nitric oxide regulates large artery stiffness and we believe that other endothelial mediators are also important regulators. Therefore, we aim to explore this in a series of studies. Regulation of stiffness of large arteries will improve treatment of age-related cardiovascular disease (eg isolated systolic hypertension)Read moreRead less
Structural Determinants of an Intracellular Calcium Store. Understanding the molecular interactions between key proteins in calcium signalling in muscle and the heart will allow calcium signalling to be used as a platform for a variety of purposes. These include reducing the debilitating effects of changes in calcium signalling and muscle performance in aging and in genetically- or drug-induced disorders. The project will have benefits for Australian biotechnology since it will facilitate the de ....Structural Determinants of an Intracellular Calcium Store. Understanding the molecular interactions between key proteins in calcium signalling in muscle and the heart will allow calcium signalling to be used as a platform for a variety of purposes. These include reducing the debilitating effects of changes in calcium signalling and muscle performance in aging and in genetically- or drug-induced disorders. The project will have benefits for Australian biotechnology since it will facilitate the design of novel compounds for treating muscle disorders in animals and humans, for improving meat quality and for use as insecticides. The project will facilitate graduate and undergraduate training in basic science with exposure to biotechnology, through our commercial partner Biotron.Read moreRead less
How triadin and junctin communicate with ryanodine receptors deep within a calcium store to determine skeletal muscle contraction. The project results will provide a platform for muscle relaxants and other drugs that will specifically target either the heart or skeletal muscle and will have applications in the livestock, veterinary and pharmaceutical Industries. The project falls within the National Research Priorities of Promoting and Maintaining Good Health and Frontier Technologies for Buil ....How triadin and junctin communicate with ryanodine receptors deep within a calcium store to determine skeletal muscle contraction. The project results will provide a platform for muscle relaxants and other drugs that will specifically target either the heart or skeletal muscle and will have applications in the livestock, veterinary and pharmaceutical Industries. The project falls within the National Research Priorities of Promoting and Maintaining Good Health and Frontier Technologies for Building and Transforming Australian Industries, as well as the national priority goal of Ageing well, Ageing Productively. The project will be of national benefit in training undergraduate students, PhD students and a postdoctoral fellow in state-of-the-art techniques in an internationally competitive research field.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