Examining novel cell signalling in the regulation of platelet structure and function. Pharmaceutical inhibition of platelet function is the primary therapy for prevention of arterial thrombosis – the most common cause of death and disability in Australia. However, current therapies have limited efficacy. Defining platelet activation mechanisms in order to rationalise more effective antithrombotic approaches is the major focus of this research. This project describes the first studies to examine ....Examining novel cell signalling in the regulation of platelet structure and function. Pharmaceutical inhibition of platelet function is the primary therapy for prevention of arterial thrombosis – the most common cause of death and disability in Australia. However, current therapies have limited efficacy. Defining platelet activation mechanisms in order to rationalise more effective antithrombotic approaches is the major focus of this research. This project describes the first studies to examine the importance of a family of intracellular signalling enzymes, the Class II phosphoinositide 3-kinases, in platelet function. These studies will define the contribution of these enzymes to platelet production and function and will establish whether their inhibition is an attractive strategy for the prevention of arterial thrombosis.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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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
Assessing a model of the physiological changes at arousal from sleep. Arousals from sleep are common in the elderly and have adverse consequences. This project will investigate a model of the changes in bodily processes (muscle, brain and cardiovascular activation) that occur when humans awaken from sleep.
Tissue Engineering of Human Heart Valve Grown In Vitro. Tissue engineering (TE) of heart valves is a new approach to cultivate a functional heart valve from human autologous cells. This innovative study aims to develop the technology to transplant cells onto a 3D biocompatible valve scaffold that is capable of mimicking native valve. The work proposed is a ground breaking study that will encompass development of a new biomaterial, manufacture of scaffolds using the Fused Deposition Modelling ra ....Tissue Engineering of Human Heart Valve Grown In Vitro. Tissue engineering (TE) of heart valves is a new approach to cultivate a functional heart valve from human autologous cells. This innovative study aims to develop the technology to transplant cells onto a 3D biocompatible valve scaffold that is capable of mimicking native valve. The work proposed is a ground breaking study that will encompass development of a new biomaterial, manufacture of scaffolds using the Fused Deposition Modelling rapid prototyping process, hemodynamic optimisation and in vitro cell culture. This will advance our knowledge in cellular and scaffold technologies and may ultimately lead to the development of a TE heart valve.Read moreRead less
Rapid Development of Biocompatible Stent Grafts for Aortic Aneurysms. Weakening of the aorta may cause an aneurysm. The present technique of its treatment involves replacing the weakened portion of the aorta with a synthetic graft. Failure of this treatment often occurs due to non-compatibility of the stent graft with natural aorta. One possible reason for this is a mismatch between elastic natural aorta and the non-elastic artificial graft. The core component of our project is the selection and ....Rapid Development of Biocompatible Stent Grafts for Aortic Aneurysms. Weakening of the aorta may cause an aneurysm. The present technique of its treatment involves replacing the weakened portion of the aorta with a synthetic graft. Failure of this treatment often occurs due to non-compatibility of the stent graft with natural aorta. One possible reason for this is a mismatch between elastic natural aorta and the non-elastic artificial graft. The core component of our project is the selection and development of a suitable biomaterial and optimization of the stent design based on hemodynamics flow analysis and its fabrication with the Fused Deposition Modelling (FDM) process.Read moreRead less
In Vitro Study of Hemodynamic Stresses and Endothelialization of Artificial Coronary Arteries. Restenosis (recurrence of the disease) is a major problem in the case of patients undergoing artificial artery by-pass surgery. Ideally the design for manufacturing the scaffold for cell adhesion of the artery should factor in hemodynamic forces and optimised geometry to withstand the hemodynamic stresses and other forces. This project aims to investigate the material for manufacturing the artificial a ....In Vitro Study of Hemodynamic Stresses and Endothelialization of Artificial Coronary Arteries. Restenosis (recurrence of the disease) is a major problem in the case of patients undergoing artificial artery by-pass surgery. Ideally the design for manufacturing the scaffold for cell adhesion of the artery should factor in hemodynamic forces and optimised geometry to withstand the hemodynamic stresses and other forces. This project aims to investigate the material for manufacturing the artificial artery using Fused Deposition Modeling and to develop methods for the establishment of endothelium on the artificial artery, concluding a restenosis-free solution for by-pass surgery. The knowledge gained through this work would be applicable to the design of other prosthetic devices.Read moreRead less
How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information i ....How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information is essential to understand how blood pressure is controlled under healthy conditions.Read moreRead less