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Biochemistry of tropoelastin and elastin. Elastin is the main protein responsible for the elasticity of vertebrate tissues. The Weiss Lab makes large quantities of full-length tropoelastin, which is crosslinked to make elastin. We want to examine the biochemistry of tropoelastin, learn how its domains participate in elastin structure and assembly, and explore cellular responses to our synthetic elastin biomaterial. Remarkably little is known of this biochemistry because elastin is a highly cross ....Biochemistry of tropoelastin and elastin. Elastin is the main protein responsible for the elasticity of vertebrate tissues. The Weiss Lab makes large quantities of full-length tropoelastin, which is crosslinked to make elastin. We want to examine the biochemistry of tropoelastin, learn how its domains participate in elastin structure and assembly, and explore cellular responses to our synthetic elastin biomaterial. Remarkably little is known of this biochemistry because elastin is a highly cross-linked and substantially insoluble macroscopic network of tropoelastin multimers. Our availability of tropoelastin and synthetic elastin now makes these studies possible.Read moreRead less
Biomedical Applications of Self-Mixing Sensors based on Vertical-Cavity Surface-Emitting Laser Arrays. The Vertical-Cavity Surface-Emitting Laser (VCSEL) is a new optical device of choice for high speed optical data networks. We propose that this communications technology can be used as a platform to develop a completely new family of sensors ideally suited to medical monitoring. Specifically, we will develop VCSEL based technology for measurement of heart activity and sensing of blood flow in ....Biomedical Applications of Self-Mixing Sensors based on Vertical-Cavity Surface-Emitting Laser Arrays. The Vertical-Cavity Surface-Emitting Laser (VCSEL) is a new optical device of choice for high speed optical data networks. We propose that this communications technology can be used as a platform to develop a completely new family of sensors ideally suited to medical monitoring. Specifically, we will develop VCSEL based technology for measurement of heart activity and sensing of blood flow in skin and tissues. This will provide novel sensors for heart monitoring and imaging, and management of skin disorders (burns and cancer).Read moreRead less
Characterisation of the oxygen-sensing asparaginyl hydroxylase, FIH-1, and hydroxylase-specific antagonists. This research will provide fundamental information on how cells and whole organisms can sense and respond accordingly to oxygen deficiency. This information is fundamental for our understanding of embryo development and adult life in different environments, and central to the diagnosis and treatment of diseases such as stroke, cardiovascular disease, and cancer. This research will contrib ....Characterisation of the oxygen-sensing asparaginyl hydroxylase, FIH-1, and hydroxylase-specific antagonists. This research will provide fundamental information on how cells and whole organisms can sense and respond accordingly to oxygen deficiency. This information is fundamental for our understanding of embryo development and adult life in different environments, and central to the diagnosis and treatment of diseases such as stroke, cardiovascular disease, and cancer. This research will contribute to our basic knowledge of these processes, provide invaluable information about the specific genes and proteins involved, and provide direct information about the therapeutic potential of specific drugs or inhibitors designed to target this oxygen response in human disease.Read moreRead less
Biochemistry of tropoelastin and elastin: the molecular architecture of elastic fibre assembly. Elastin destruction drives the progression of emphysema, a major component of chronic obstructive pulmonary disease which is a major cause of death. Loss of elastin leads to profound blockage of arteries. If we are to treat these problems we need to know how to make and repair elastin. This research will enable us to discover how elastin is constructed and define its interacting partners. We will lear ....Biochemistry of tropoelastin and elastin: the molecular architecture of elastic fibre assembly. Elastin destruction drives the progression of emphysema, a major component of chronic obstructive pulmonary disease which is a major cause of death. Loss of elastin leads to profound blockage of arteries. If we are to treat these problems we need to know how to make and repair elastin. This research will enable us to discover how elastin is constructed and define its interacting partners. We will learn how to make tissue components found in parts of the body that expand and contract such as the arteries, lung and skin. We will learn about the molecular mechanisms of elastin assembly and cell interactions, which gives us the core molecular toolkit to repair elastin tissue.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
Free Radicals in Chemistry and Biology: A Computational Quantum Chemistry Investigation. This proposal aims to carry out state-of-the-art chemistry research using computers rather than traditional laboratory techniques. Free radicals, which have widespread importance in the multibillion dollar polymer and health industries, form the centrepiece of the proposal. These are highly reactive substances that are difficult to study by conventional experimental techniques but ideal to study using compu ....Free Radicals in Chemistry and Biology: A Computational Quantum Chemistry Investigation. This proposal aims to carry out state-of-the-art chemistry research using computers rather than traditional laboratory techniques. Free radicals, which have widespread importance in the multibillion dollar polymer and health industries, form the centrepiece of the proposal. These are highly reactive substances that are difficult to study by conventional experimental techniques but ideal to study using computers. The increased understanding of free radicals that will stem from this research may help in dealing with ageing, and afflictions such as hardening of the arteries and vitamin B12 deficiency. It will also result in the training at the highest level of new generations of chemists in this exciting field of "chemistry with computers".Read moreRead less
Computational Quantum Chemistry Study of Molecular Structures, Stabilities and Reactions. Computational quantum chemistry is revolutionizing the study and practice of chemistry. We will use state-of-the-art computer calculations to investigate chemical structures, stabilities and reactions, particularly for free radicals. Radicals are of great importance in chemistry, biology and polymer science, but are difficult to study experimentally. We will use the computer calculations to determine how ....Computational Quantum Chemistry Study of Molecular Structures, Stabilities and Reactions. Computational quantum chemistry is revolutionizing the study and practice of chemistry. We will use state-of-the-art computer calculations to investigate chemical structures, stabilities and reactions, particularly for free radicals. Radicals are of great importance in chemistry, biology and polymer science, but are difficult to study experimentally. We will use the computer calculations to determine how to make radicals more stable, how they react to produce polymers, how they cause damage to proteins, and how they are involved in helping vitamin B12 make reactions go faster. We will create new methodologies in order to reliably achieve these goals.Read moreRead less
Investigating the molecular function of alpha-Haemoglobin stabilising protein. The research described in this proposal will provide new insights into haemoglobin regulation and redox chemistry in erythrocytes. Deregulation of these processes gives rise to a number of debilitating diseases, including varieties of anaemia and thalassaemia-in Australia it is estimated that 3% of the population could be carriers of b-thalassaemia mutations. Given the contribution of free aHb to the pathology of b-th ....Investigating the molecular function of alpha-Haemoglobin stabilising protein. The research described in this proposal will provide new insights into haemoglobin regulation and redox chemistry in erythrocytes. Deregulation of these processes gives rise to a number of debilitating diseases, including varieties of anaemia and thalassaemia-in Australia it is estimated that 3% of the population could be carriers of b-thalassaemia mutations. Given the contribution of free aHb to the pathology of b-thalassaemia, understanding the specific aHb-binding factor, AHSP is a goal of national significance. In the long term, manipulation of AHSP function through gene therapy may have a direct role in the treatment of thalassaemia.Read moreRead less