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
Guanylate cyclases - an expanding family critical in plant growth and development. The enzyme guanylate cyclase (GC) forms an important signalling molecule. We have identified unique GC molecules from higher plants. We shall use strategic basic research to determine the biological importance of these novel molecules in plant growth and development. We have formed an international team to achieve these goals and also to develop strong scientific links between Australia and other countries such as ....Guanylate cyclases - an expanding family critical in plant growth and development. The enzyme guanylate cyclase (GC) forms an important signalling molecule. We have identified unique GC molecules from higher plants. We shall use strategic basic research to determine the biological importance of these novel molecules in plant growth and development. We have formed an international team to achieve these goals and also to develop strong scientific links between Australia and other countries such as South Africa. The outcomes will provide new insight into the biological function of the novel GCs. Consequently, the new knowledge is critical to the development of novel biotechnological approaches to benefit sustainable agriculture in Australia.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.
Read moreRead less
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
Molecular pumps and metabolism: regulatory interactions that control metal uptake and metabolism in bacteria. ABC (ATP-Binding Cassette) transporters are ubiquitous pumps that transport small molecules into and out of cells. This project investigates the novel roles of small-molecule-binding domains in the protein machine that drives the transporters for molybdenum and iron. They are predicted to interact with regulatory proteins and integrate transport with metabolism. It will provide insights ....Molecular pumps and metabolism: regulatory interactions that control metal uptake and metabolism in bacteria. ABC (ATP-Binding Cassette) transporters are ubiquitous pumps that transport small molecules into and out of cells. This project investigates the novel roles of small-molecule-binding domains in the protein machine that drives the transporters for molybdenum and iron. They are predicted to interact with regulatory proteins and integrate transport with metabolism. It will provide insights into metal trafficking and characterize gene regulatory networks that are important for bacterial pathogenicity and biological nitrogen fixation.Read moreRead less
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
Host cell targets of bacterial virulence effectors. The research described in this proposal will result in a better understanding of the cell biology of host-pathogen interactions. We are in a unique position to analyze the importance of protein/protein interactions between bacterial virulence determinants and host cell proteins using a range of cell biology techniques to address the fundamental, molecular basis of the host-pathogen interaction. In addition we will construct a new genetic tool ....Host cell targets of bacterial virulence effectors. The research described in this proposal will result in a better understanding of the cell biology of host-pathogen interactions. We are in a unique position to analyze the importance of protein/protein interactions between bacterial virulence determinants and host cell proteins using a range of cell biology techniques to address the fundamental, molecular basis of the host-pathogen interaction. In addition we will construct a new genetic tool to identify novel bacterial virulence determinants. We anticipate that a greater knowledge of the factors that contribute to the host-pathogen interaction will provide new insights into the subversion of host cell processes by bacterial pathogens of animals, plants and humans.
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