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
Regenerating lizard tails: A model for understanding the process of lymphangiogenesis. In humans, impaired lymphatic drainage in limbs causes the debilitating swelling termed lymphoedema. Lymphoedema affects 500,000,000 people worldwide. In the developed world lymphoedema predominantly results from surgery for cancer, and occurs in approximately 25% of breast cancer patients. We will examine lymph vessel regeneration (lymphangiogenesis) in a naturally regenerating, complex structure (the lizard ....Regenerating lizard tails: A model for understanding the process of lymphangiogenesis. In humans, impaired lymphatic drainage in limbs causes the debilitating swelling termed lymphoedema. Lymphoedema affects 500,000,000 people worldwide. In the developed world lymphoedema predominantly results from surgery for cancer, and occurs in approximately 25% of breast cancer patients. We will examine lymph vessel regeneration (lymphangiogenesis) in a naturally regenerating, complex structure (the lizard tail), to describe the regrowth process and determine the abundance, location, functional properties and molecular control of the new lymphatics. Furthermore, if reptilian lymphatic growth factors can promote lymphangiogenesis in mammals, we can design novel therapeutic approaches using reptilian ligands to promote lymphangiogenesis in lymphoedematous human tissues.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
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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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
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
Muscling in on the brain. This project investigates an enzyme that 'matures' neurotransmitters in the brain that regulate food intake, energy expenditure and blood pressure by the brain; these neurotransmitters arise from the same precursor molecule. This project will show the physiological relevance of this enzyme in obesity.
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
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