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
Biophysical characterization of protein interactions within a transcription factor network. Gene expression is regulated in part by interactions between pairs and groups of proteins known as transcription factors and co-regulators. These proteins assemble into complexes at gene promoters and enhancers and thereby control the expression of that gene. Little is known at the molecular level of how these complexes form and how different interactions cooperate or compete with each other. In this prop ....Biophysical characterization of protein interactions within a transcription factor network. Gene expression is regulated in part by interactions between pairs and groups of proteins known as transcription factors and co-regulators. These proteins assemble into complexes at gene promoters and enhancers and thereby control the expression of that gene. Little is known at the molecular level of how these complexes form and how different interactions cooperate or compete with each other. In this proposal we aim to define a complex between two transcriptional regulators (HOP and SRF) involved in cardiac development and to begin to define other interactions that make up a transcriptional network essential for development of a normal heart.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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Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883032
Funder
Australian Research Council
Funding Amount
$1,300,000.00
Summary
800 MHz NMR spectrometer for biomolecular structure-function analysis. An understanding of how organisms function at the molecular level is central to developing the ability to fight many diseases in a rational way. This equipment will provide the capability for many different laboratories around NSW and the ACT to advance our knowledge at this fundamental level, primarily by examining the structures and functions of biomolecules such as proteins.
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
Defining the Regulatory Pool of Cholesterol in the Mammalian Cell. Heart disease remains the greatest killer of Australians and Alzheimer's disease represents a growing burden in our aging population. The information gained in this project will be invaluable in advancing our understanding of how cholesterol levels are controlled within the cell and will provide the groundwork for further research that can help to identify novel targets for new drugs to fight heart disease and Alzheimer's diseas ....Defining the Regulatory Pool of Cholesterol in the Mammalian Cell. Heart disease remains the greatest killer of Australians and Alzheimer's disease represents a growing burden in our aging population. The information gained in this project will be invaluable in advancing our understanding of how cholesterol levels are controlled within the cell and will provide the groundwork for further research that can help to identify novel targets for new drugs to fight heart disease and Alzheimer's disease.Read moreRead less
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