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.
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
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
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
Gene regulatory networks in heart development. In humans, structural and functional malformations of the heart are very common and are associated with a high economic and emotional burden. In this project, we will study how genetic networks initiate and control heart development at a molecular level. We will establish and employ state-of-the-art technologies and bioinformatics tools to explore the function of cardiac regulatory genes in detail. Our work will contribute both to discover new cardi ....Gene regulatory networks in heart development. In humans, structural and functional malformations of the heart are very common and are associated with a high economic and emotional burden. In this project, we will study how genetic networks initiate and control heart development at a molecular level. We will establish and employ state-of-the-art technologies and bioinformatics tools to explore the function of cardiac regulatory genes in detail. Our work will contribute both to discover new cardiac pathways for a better understanding of heart formation and disease, and to develop advanced techniques that will contribute to strengthen Australian basic and strategic research.Read moreRead less
Heparan sulfate proteoglycan from smooth muscle cell basal lamina: It's role in cell signalling. Heart disease is the major killer of people in the Western world. central to this disease is the killing of heart muscle tissue to it being starved of oxygen via a "heart attack". One of the common treatments is coronary artery bypass surgery, however, the supply of vessels that can be used is limited. In order to provide an alternative supply of vessels, we are aiming to engineer blood vessels i ....Heparan sulfate proteoglycan from smooth muscle cell basal lamina: It's role in cell signalling. Heart disease is the major killer of people in the Western world. central to this disease is the killing of heart muscle tissue to it being starved of oxygen via a "heart attack". One of the common treatments is coronary artery bypass surgery, however, the supply of vessels that can be used is limited. In order to provide an alternative supply of vessels, we are aiming to engineer blood vessels in the laboratory. The major cell of the wall of arteries, the smooth muscle cell, is critical to normal functioning and integration of these transplanted arteries. To do this we will need to understand the cell signalling responses of these cells in relation to molecules in their surrounding environment.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100010
Funder
Australian Research Council
Funding Amount
$720,000.00
Summary
A 5-D Correlative Imaging Platform: Combining the strengths of light and electron microscopy. This will be Australia's first dedicated five-dimensional multiphoton-microscopy platform, allowing observation of dynamic structures across different length and time scales under controlled temperatures, followed by high-resolution electron microscopy studies on the same samples. This platform will provide a unique characterisation tool to Australia's top-flight investigators, and so contribute to the ....A 5-D Correlative Imaging Platform: Combining the strengths of light and electron microscopy. This will be Australia's first dedicated five-dimensional multiphoton-microscopy platform, allowing observation of dynamic structures across different length and time scales under controlled temperatures, followed by high-resolution electron microscopy studies on the same samples. This platform will provide a unique characterisation tool to Australia's top-flight investigators, and so contribute to the nation's research priorities. It will enable: fundamental studies of cancer, neural diseases and immune disorders; the development of frontier technologies, such as smart nanomaterials, biosensors and targeted drug delivery; and applied research to help plants and soils adapt to climate variability, and to increase sustainable use of water.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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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
Mechanisms and consequences of oxidation of glycosaminoglycans, proteins and proteoglycans by myeloperoxidase-derived oxidants. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation r ....Mechanisms and consequences of oxidation of glycosaminoglycans, proteins and proteoglycans by myeloperoxidase-derived oxidants. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation reactions in weakening the structure of lesions and making them prone to rupture. Little is known about the fundamental chemistry of such damage; this will be addressed in the proposed program. The data obtained will underpin the development of new preventative and protective strategies to minimise lesion rupture and deaths from this major disease.Read moreRead less