Molecular control of apoptosis and protein homeostasis. A million cells are produced every second by cell division. At the same time a million cells commit suicide by a process called apoptosis. When cells fail to die when they should they can develop into cancers. In heart attacks, stroke and neurodegenerative diseases, many cells appear to activate their self destruct mechanism to die unnecessarily. Drugs that can cause cancer cells to kill themselves, or drugs that prevent cells dying when th ....Molecular control of apoptosis and protein homeostasis. A million cells are produced every second by cell division. At the same time a million cells commit suicide by a process called apoptosis. When cells fail to die when they should they can develop into cancers. In heart attacks, stroke and neurodegenerative diseases, many cells appear to activate their self destruct mechanism to die unnecessarily. Drugs that can cause cancer cells to kill themselves, or drugs that prevent cells dying when they shouldn't, would make a major impact on many important diseases. Understanding the molecular mechanisms of cell death is the first step towards developing these drugs.Read moreRead less
Development of Model Systems to Investigate Blood Hydrodynamic Parameters Affecting Blood Cell Function: An Interdisciplinary Approach. National benefit will come through this research contributing to a better understanding of blood flow biology and pathology, both of which are of particular relevance to the aging Australian population. This benefit is well aligned with the 2008 National research priority 2: Promoting and Maintaining Good Health; Priority Goal 3. Preventative Health. The synthes ....Development of Model Systems to Investigate Blood Hydrodynamic Parameters Affecting Blood Cell Function: An Interdisciplinary Approach. National benefit will come through this research contributing to a better understanding of blood flow biology and pathology, both of which are of particular relevance to the aging Australian population. This benefit is well aligned with the 2008 National research priority 2: Promoting and Maintaining Good Health; Priority Goal 3. Preventative Health. The synthesis of both extensive expertise in platelet/cardiovascular research and bioengineering/rheology should provide a substantial platform from which fundamental new discoveries in this niche area can be made. The development of novel platelet analysis tools arising from this work may also ultimately lead to new intellectual property and attract industry based funding.Read moreRead less
Examination of the Calcium Signalling Dynamics Linked to Integrin Adhesion Utilising a Novel Micro-imaging System. This study aims at increasing our understanding of the fundamental cell processes that allow cells to adhere to surfaces. The proposed study will lead to a greater understanding of the calcium signalling mechanisms that are fundamental to diverse biological phenomena such as, tissue regeneration and repair, blood clotting, cancer metastasis, and neuronal cell function. From a preven ....Examination of the Calcium Signalling Dynamics Linked to Integrin Adhesion Utilising a Novel Micro-imaging System. This study aims at increasing our understanding of the fundamental cell processes that allow cells to adhere to surfaces. The proposed study will lead to a greater understanding of the calcium signalling mechanisms that are fundamental to diverse biological phenomena such as, tissue regeneration and repair, blood clotting, cancer metastasis, and neuronal cell function. From a preventative health perspective, the investigation of platelet calcium signalling will greatly accelerate the development of new pharmaceuticals to tackle acute and chronic cardiovascular diseases, such as stroke, heart attack and artherosclerosis. 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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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
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
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
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
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
Studies of the pi3-kinase enzyme family using selective inhibitors. The objective of this project is to study the function of the PI3-kinase enzyme family in blood platelets. To do this, inhibitors which block the action of specific family members, will be evaluated for their effects in assays of platelet function. The results will enhance our understanding of the way in which platelets and other cells respond to stimuli, and lead new approaches to designing novel drugs that block these response ....Studies of the pi3-kinase enzyme family using selective inhibitors. The objective of this project is to study the function of the PI3-kinase enzyme family in blood platelets. To do this, inhibitors which block the action of specific family members, will be evaluated for their effects in assays of platelet function. The results will enhance our understanding of the way in which platelets and other cells respond to stimuli, and lead new approaches to designing novel drugs that block these responses.Read moreRead less