Structural studies on the mitochondrial protein import machinery. Proteins transported across biological membranes are generally synthesized as precursors with signal sequences. These signal sequences are decoded by one of a number of membrane-specific protein transport machinery, but how this decoding occurs is largely unknown. This proposal aims to understand the structural basis of protein import into the mitochondrion, a poorly understood biological process. This study will enhance signif ....Structural studies on the mitochondrial protein import machinery. Proteins transported across biological membranes are generally synthesized as precursors with signal sequences. These signal sequences are decoded by one of a number of membrane-specific protein transport machinery, but how this decoding occurs is largely unknown. This proposal aims to understand the structural basis of protein import into the mitochondrion, a poorly understood biological process. This study will enhance significantly our understanding of mitochondrial biology, and will also have ramifications for other areas of protein transport.Read moreRead less
Regulation of the actin cytoskeleton by LIM kinase 2. Because the regulation of actin cytoskeleton is essential for many cellular processes including cell motility and the normal function of neurons, it is of great importance to understand its regulation. Elucidation of the molecular and biological mechanisms underlying the actin cytoskeleton including cell motility may enable the identification of novel therapeutic targets for the treatment of diseases such as cancer metastasis, Alzheimer disea ....Regulation of the actin cytoskeleton by LIM kinase 2. Because the regulation of actin cytoskeleton is essential for many cellular processes including cell motility and the normal function of neurons, it is of great importance to understand its regulation. Elucidation of the molecular and biological mechanisms underlying the actin cytoskeleton including cell motility may enable the identification of novel therapeutic targets for the treatment of diseases such as cancer metastasis, Alzheimer disease (AD) and/or Multiple Sclerosis (MS) in which the regulation of the actin cytoskeleton is affected.
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Analysis of the Role of Snapin in the Regulation of SNARE Complex Assembly. The aims of the proposed studies are to investigate the role played by a protein, snapin in the trafficking of membranes and cargo proteins between different compartments inside mammalian cells. Membrane trafficking is a fundamental cellular process that requires a family of related molecules termed SNARES. We have recently discovered that snapin interacts with certain members of the SNARE family, implying a critical rol ....Analysis of the Role of Snapin in the Regulation of SNARE Complex Assembly. The aims of the proposed studies are to investigate the role played by a protein, snapin in the trafficking of membranes and cargo proteins between different compartments inside mammalian cells. Membrane trafficking is a fundamental cellular process that requires a family of related molecules termed SNARES. We have recently discovered that snapin interacts with certain members of the SNARE family, implying a critical role in membrane trafficking. The proposed studies will provide important new insights into the molecular mechanisms underlying the function of both snapin and SNAREs, and membrane trafficking in general.Read moreRead less
How protein tyrosine phosphatases select their substrates. Protein tyrosine phosphatases (PTPs) are enzymes that control the response of cells to divergent environmental stimuli. This project will determine how individual PTPs exert selective effects on cellular communication networks to coordinate organismal development, growth and survival.
Ribonucleic acid (RNA)-binding proteins regulate protein targeting and organelle biosynthesis. We will investigate a new paradigm in biology: the coordination of protein expression in space and time. Detailed knowledge will be gained about proteins that perform important roles in ensuring the proliferative potential of cells an essential aspect of stem cell biology, regenerative medicine and development of cancer. The study combines skills in several aspects of genetics, biochemistry and molecul ....Ribonucleic acid (RNA)-binding proteins regulate protein targeting and organelle biosynthesis. We will investigate a new paradigm in biology: the coordination of protein expression in space and time. Detailed knowledge will be gained about proteins that perform important roles in ensuring the proliferative potential of cells an essential aspect of stem cell biology, regenerative medicine and development of cancer. The study combines skills in several aspects of genetics, biochemistry and molecular cell biology and will therefore provide excellent training opportunities for PhD students and postdoctoral fellows in an internationally highly competitive field of research.Read moreRead less
The functional organisation of the trans-Golgi network: From cultured cells to physiological systems. This research will result in a better understanding of the secretory pathway of all eukaryotic cells, a process of broad biological and biomedical significance. It will impact on cell biology in the broadest sense, from membrane biogenesis to lipid domain organization, as well as membrane transport, protein structure and protein targeting. Furthermore, this work will utilize and develop fronti ....The functional organisation of the trans-Golgi network: From cultured cells to physiological systems. This research will result in a better understanding of the secretory pathway of all eukaryotic cells, a process of broad biological and biomedical significance. It will impact on cell biology in the broadest sense, from membrane biogenesis to lipid domain organization, as well as membrane transport, protein structure and protein targeting. Furthermore, this work will utilize and develop frontier technologies of live cell imaging and RNA interference as a genetic tool to investigate functions of a protein family. By training post-graduate students and post-doctoral staff, it will contribute to the expertise of cell biology in Australia. International collaborations will enhance connections between Australia and overseas research.Read moreRead less
The structure and function of the trans-Golgi network: role of golgins and G proteins. This research will provide a better understanding of the secretory pathway of all eukaryotic cells, a process of broad biological and biomedical significance. It will also contribute to a better understanding of how a cell works, including how cell membranes are organization, how the transport processes of the cell are regulated and how proteins are targeted to their intracellular destination. Further, this ....The structure and function of the trans-Golgi network: role of golgins and G proteins. This research will provide a better understanding of the secretory pathway of all eukaryotic cells, a process of broad biological and biomedical significance. It will also contribute to a better understanding of how a cell works, including how cell membranes are organization, how the transport processes of the cell are regulated and how proteins are targeted to their intracellular destination. Further, this work will utilize the frontier technology of RNA interference as a genetic tool to investigate functions of genes. By training post-graduate students and post-doctoral staff, it will contribute to the expertise of cell biology in Australia. International collaborations will enhance connections with overseas researchers.Read moreRead less
Intracellular localisation of insulin signalling proteins in human skeletal muscle following exercise. The metabolic action of insulin in skeletal muscle is enhanced by exercise, but the underlying mechanisms mediating this are unknown. Insulin receptor substrate proteins are key mediators in the intracellular insulin signalling pathway and play a central role in regulating many metabolic events. Our aim is to examine the hypothesis that exercise induces a novel subcellular redistribution of the ....Intracellular localisation of insulin signalling proteins in human skeletal muscle following exercise. The metabolic action of insulin in skeletal muscle is enhanced by exercise, but the underlying mechanisms mediating this are unknown. Insulin receptor substrate proteins are key mediators in the intracellular insulin signalling pathway and play a central role in regulating many metabolic events. Our aim is to examine the hypothesis that exercise induces a novel subcellular redistribution of these insulin receptor substrate proteins in skeletal muscle, such that the metabolic action of insulin is enhanced. Elucidating the mechanisms whereby exercise enhances insulin action underpins the development of new treatments and therapies with the aim of improving skeletal muscle function in health and disease.Read moreRead less
The role of a novel family of Golgi proteins in maintaining the structure and function of the trans-Golgi network. The secretory pathway of eukaryotic cells is fundamental for proper cell growth. The Golgi apparatus is a key organelle of this pathway where newly made proteins are selectively packaged into membrane-bound transport vehicles and then shipped to their correct destination, such as the surface of the cell. This research aims to understand the mechanism by which these cargo-loaded tr ....The role of a novel family of Golgi proteins in maintaining the structure and function of the trans-Golgi network. The secretory pathway of eukaryotic cells is fundamental for proper cell growth. The Golgi apparatus is a key organelle of this pathway where newly made proteins are selectively packaged into membrane-bound transport vehicles and then shipped to their correct destination, such as the surface of the cell. This research aims to understand the mechanism by which these cargo-loaded transport vehicles are generated from the Golgi apparatus. This information is of fundamental importance in understanding how a cell survives and grows, and is necessary to allow a rational basis for the engineering of secreted recombinant molecules.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100157
Funder
Australian Research Council
Funding Amount
$600,000.00
Summary
Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information th ....Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information that is not easily obtainable with other approaches. The project will enable Australian researchers to image and analyse the full complexity of biological systems, potentially transforming cell biology, drug development and understanding the molecular basis of disease. It will also demonstrate how the capacity of microscopy facilities can be enhanced and bias in imaging data reduced by automating data acquisition and mining of image-based data.Read moreRead less