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 MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with res ....The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with respect to transcriptional elongation and long-range regulation. It will highlight a new approach to the therapeutic targeting of MYB in cancer: data generated from this research may enable us to target MYB expression in a range of cancers including breast cancer by inhibiting transcriptional elongation. And it will provide training in advanced molecular biology to postdoctoral scientists and students.Read moreRead less
Regulation of nuclear localisation of the AreA transcription factor in Aspergillus nidulans. An understanding of the means by which the expression of genes is regulated is of fundamental significance. Changes in gene expression are central to the development, growth and viability of all cells and their response to environmental changes/stresses. This study uses the fungus Aspergillus nidulans as an excellent molecular genetic tool to investigate how a key regulatory protein controls gene expres ....Regulation of nuclear localisation of the AreA transcription factor in Aspergillus nidulans. An understanding of the means by which the expression of genes is regulated is of fundamental significance. Changes in gene expression are central to the development, growth and viability of all cells and their response to environmental changes/stresses. This study uses the fungus Aspergillus nidulans as an excellent molecular genetic tool to investigate how a key regulatory protein controls gene expression in response to nitrogen starvation stress. Our understanding of these dynamic processes informs our approaches to the development of cancer therapies, to commercial biotechnology application and to control of human, plant and animal pathogens in which the infectious process is triggered by environmental stress. Read moreRead less
Developmental Switches: Nuclear Transport and Spermatogenesis. We propose to test the novel hypothesis that changes in the nuclear import machinery are a key facet of cellular differentiation. We will investigate a new paradigm in developmental biology regarding whether differentiation is achieved, or can be directed, by altering transport of macromolecules, such as specific transcription factors, into the nucleus. This project will define changes in the nuclear import machinery that accomp ....Developmental Switches: Nuclear Transport and Spermatogenesis. We propose to test the novel hypothesis that changes in the nuclear import machinery are a key facet of cellular differentiation. We will investigate a new paradigm in developmental biology regarding whether differentiation is achieved, or can be directed, by altering transport of macromolecules, such as specific transcription factors, into the nucleus. This project will define changes in the nuclear import machinery that accompany germ and somatic cell differentiation in the developing and adult mammalian testis. This will be linked to changes in the function of key proteins acting within the nucleus using both in vitro and in vivo approaches.
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Novel roles for importin alpha proteins in the nucleus. The project will provide fundamental new information about how changes in cell function are influenced by importin (IMP) alpha proteins, both through changes in gene transcription and through alterations to intracellular transport. These findings will inform areas of national priority that include Aging Well, Aging Productively with specific regard to cellular stress responses, and A Healthy Start to Life in the context of production of hea ....Novel roles for importin alpha proteins in the nucleus. The project will provide fundamental new information about how changes in cell function are influenced by importin (IMP) alpha proteins, both through changes in gene transcription and through alterations to intracellular transport. These findings will inform areas of national priority that include Aging Well, Aging Productively with specific regard to cellular stress responses, and A Healthy Start to Life in the context of production of healthy, genetically intact sperm. This project draws together an international team to investigate a phenomenon with implications for new understanding of normal developmental processes and the response of cells/tissues to disease conditions.Read moreRead less
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.
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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
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