Structure and function of the protein translocation channels in the mitochondrial outer membrane. Biological membranes are the basis of life and understanding how proteins are inserted into membranes is a major goal in the Biological Sciences. The TOM complex is a molecular machine mediating protein insertion into a biological membrane. Recent successes with X-ray diffraction of protein crystals, and solution and solid-state NMR spectroscopy have heralded leaps-and-bound advances for our knowled ....Structure and function of the protein translocation channels in the mitochondrial outer membrane. Biological membranes are the basis of life and understanding how proteins are inserted into membranes is a major goal in the Biological Sciences. The TOM complex is a molecular machine mediating protein insertion into a biological membrane. Recent successes with X-ray diffraction of protein crystals, and solution and solid-state NMR spectroscopy have heralded leaps-and-bound advances for our knowledge of how membranes work at the molecular level. Using a combination of phylogenetic analysis, yeast genetics and these new techniques from structural biology, we will characterize the structure and function of the core from the TOM complex.Read moreRead less
Multiplexed Molecular Reading of Protein Associations via Nanoscaled Devices. Current developments in Nanoscience and Nanotechnology hold many promises in terms of revolutionising our industrial base, transforming biology, medical science and practice. This project strives to achieve some of these goals by, for the first time, building and testing nano-scaled devices with the capability to rapidly ?read? information about complex protein associations. With the recent completion of the Human Ge ....Multiplexed Molecular Reading of Protein Associations via Nanoscaled Devices. Current developments in Nanoscience and Nanotechnology hold many promises in terms of revolutionising our industrial base, transforming biology, medical science and practice. This project strives to achieve some of these goals by, for the first time, building and testing nano-scaled devices with the capability to rapidly ?read? information about complex protein associations. With the recent completion of the Human Genome project, major opportunities exist to provide spectacular advances in human health care (eg, via novel diagnostics) provided that appropriate high-throughput biological reading devices can be developed. In developing such devices, this project also aims to catalyse the Australian Nanotechnology/Biotechnology industry.Read moreRead less
A new G-protein coupled receptor target for conotoxins. We aim to understand the interaction between venom components from the marine cone snail, a major source of potential drug leads, and a key receptor in nerve cell signalling. This receptor plays a role in many nervous system functions and has been proposed as a target for treating a range of diseases including pain, depression and drug addiction. It is critical that we understand this interaction so we can fully exploit the potential of the ....A new G-protein coupled receptor target for conotoxins. We aim to understand the interaction between venom components from the marine cone snail, a major source of potential drug leads, and a key receptor in nerve cell signalling. This receptor plays a role in many nervous system functions and has been proposed as a target for treating a range of diseases including pain, depression and drug addiction. It is critical that we understand this interaction so we can fully exploit the potential of these molecules as drug leads. The potential exists for multibillion dollar markets for these new drugs that could provide significant economic benefits to Australia.Read moreRead less
Myofibroblast differentiation: from haemopoietic cells to smooth muscle. Until very recently the ability of adult cells with specific differentiated functions to re-differentiate for another function was thought to be extremely limited. However we have shown that cells ultimately derived from the bone marrow can differentiate into fibroblasts, then into myofibroblasts and then into smooth muscle cells. This project will build on these unique findings and determine the molecular mechanisms cont ....Myofibroblast differentiation: from haemopoietic cells to smooth muscle. Until very recently the ability of adult cells with specific differentiated functions to re-differentiate for another function was thought to be extremely limited. However we have shown that cells ultimately derived from the bone marrow can differentiate into fibroblasts, then into myofibroblasts and then into smooth muscle cells. This project will build on these unique findings and determine the molecular mechanisms controlling this process. We hypothesise that the local environment of a cell is critical and will involve a combination of particular extracellular matrix and growth factors as well as mechanical tension and the presence of other cell types.Read moreRead less
Factors involved in release of cytochrome c from mitochondria during apoptosis. Mitochondria are energy-producing organelles that activate cell death by selective release of constituents, notably cytochrome c, which participate in death-signalling cascades. I aim to probe such mitochondrial release mechanisms in intact cells, by focussing on features of translocated proteins relevant to release. Cultured mouse cells lacking cytochrome c are uniquely suited to these studies. A series of cytochrom ....Factors involved in release of cytochrome c from mitochondria during apoptosis. Mitochondria are energy-producing organelles that activate cell death by selective release of constituents, notably cytochrome c, which participate in death-signalling cascades. I aim to probe such mitochondrial release mechanisms in intact cells, by focussing on features of translocated proteins relevant to release. Cultured mouse cells lacking cytochrome c are uniquely suited to these studies. A series of cytochrome c derivatives will be engineered in elongated or aggregated forms and their release studied (including interactions with putative release machinery components) following death-signal activation. The project will elucidate a central mechanism in the cell death process, highly significant in many biological contexts.Read moreRead less
Identification of Proteins that Regulate Apoptosis Through Interaction With IAPS. Apoptosis is the process by which multicellular organisms eliminate unwanted cells. Identifying proteins involved in cell death regulation is central to our understanding of disease states arising from aberrations in this process. The mammalian protein DIABLO, promotes cell death by interacting with and antagonising inhibitor of apoptosis proteins (IAPS). Given the existence of several IAP regulatory proteins (IRPs ....Identification of Proteins that Regulate Apoptosis Through Interaction With IAPS. Apoptosis is the process by which multicellular organisms eliminate unwanted cells. Identifying proteins involved in cell death regulation is central to our understanding of disease states arising from aberrations in this process. The mammalian protein DIABLO, promotes cell death by interacting with and antagonising inhibitor of apoptosis proteins (IAPS). Given the existence of several IAP regulatory proteins (IRPs) in insects, other mammalian IRPs probably also exist. These may be of equal importance in regulating apoptosis, especially in tissues where DIABLO is not expressed. The main aim of the proposed study is to idenitify and characterise other IRPs in mammalian cells.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0226463
Funder
Australian Research Council
Funding Amount
$160,000.00
Summary
Fluorescence Lifetime Imaging Facility. The aim of this proposal is to establish the first fluorescence lifetime imaging facility (FLIM) in Australia. The imaging technique provided by the new facility when combined with the use of novel fluorescent protein technology will enable many different events, represented by protein-protein interactions, to be non-invasively, visualised spatially and temporally inside the living cell. The new facility will provide timely state-of -the-art infrastructu ....Fluorescence Lifetime Imaging Facility. The aim of this proposal is to establish the first fluorescence lifetime imaging facility (FLIM) in Australia. The imaging technique provided by the new facility when combined with the use of novel fluorescent protein technology will enable many different events, represented by protein-protein interactions, to be non-invasively, visualised spatially and temporally inside the living cell. The new facility will provide timely state-of -the-art infrastructure necessary for research groups to further develop and maintain their international reputations, will build stronger research collaborations between partner institutions and will attract researchers from overseas.Read moreRead less
Combined genetic and cellular analysis of melanisation to study variation in human pigmentation. This investigation examines variations in the genes that are important determinants of human skin pigmentation and are likely to be associated with skin cancer risk. Our research program will form the basis of future diagnostics based on major genes that determine a persons skin type. Current skin cancer prevention strategies rely predominantly on broad spectrum campaigns that are aimed at increasi ....Combined genetic and cellular analysis of melanisation to study variation in human pigmentation. This investigation examines variations in the genes that are important determinants of human skin pigmentation and are likely to be associated with skin cancer risk. Our research program will form the basis of future diagnostics based on major genes that determine a persons skin type. Current skin cancer prevention strategies rely predominantly on broad spectrum campaigns that are aimed at increasing the general community awareness of the damaging effects of UV radiation. A better understanding of the genetic basis of UV-sensitive skin types will greatly enhance the targeting of such skin cancer-prevention campaigns, provide an understanding of changes that occur in skin pathology, and the mechanisms of sun induced tanning.Read moreRead less
Parallel genetic and cellular analysis of melanogensis: A new paradigm to study variation in pigmentation. This is the first attempt to characterise the differences in human pigmentation using a combined genetic and cellular analysis of melanogenesis. We have the ability to culture the pigmenting cells of the human epidermis and hair follicles called melanocytes from individuals of defined genotype. This will allow us to correlate mutations in melanosomal proteins with functional defects withi ....Parallel genetic and cellular analysis of melanogensis: A new paradigm to study variation in pigmentation. This is the first attempt to characterise the differences in human pigmentation using a combined genetic and cellular analysis of melanogenesis. We have the ability to culture the pigmenting cells of the human epidermis and hair follicles called melanocytes from individuals of defined genotype. This will allow us to correlate mutations in melanosomal proteins with functional defects within the cells in culture using live cell imaging, electron microscopy and biochemical analysis. This will provide a molecular basis to explain the pigmentary characteristics of individuals allowing prediction and diagnosis of their photosensitivity with important implications for skin cancer risk.Read moreRead less