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
A novel link between plant pathogen defence and DNA repair capability. Plants and plant-based industries are essential for the provision of food, clothing and building materials and underpin the economies of rural communities. Plant yield and quality and the biodiversity of natural systems are dramatically reduced by disease. The fundamental knowledge gained from our research will enable manipulation of the factors that enhance disease resistance resulting in a significant benefit to Australian ....A novel link between plant pathogen defence and DNA repair capability. Plants and plant-based industries are essential for the provision of food, clothing and building materials and underpin the economies of rural communities. Plant yield and quality and the biodiversity of natural systems are dramatically reduced by disease. The fundamental knowledge gained from our research will enable manipulation of the factors that enhance disease resistance resulting in a significant benefit to Australian agriculture and protection of our natural resources. The current reliance for disease control on chemicals that damage the environment will be reduced and our research will contribute directly to the provision of cheaper, simpler and more effective methods of control.
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Identification of genes regulating breast cancer progression and metastasis. Breast cancer is the most common cause of cancer-related death in women in Australia. Although the treatments have improved over the last thirty years, many women still die from relapse of the disease. Our goal is to identify genes involved in the regulation of breast cancer progression and metastasis. This may lead to the discovery of druggable molecules for better targeted therapies for patients.
Biochemical, Genomic and Phenomic Analysis of Gastric Parietal Cells from Wildtype and Mutant Mice. The interface between the cell and its environment is the cell membrane. Signals, nutrients, and ions all have to cross this barrier. In addition, the cells contain many specialized intracellular membranous compartments. We know little about the signals that direct the synthesis of these structures and determine their final composition and shape. This grant will utilize acid secretory cells in the ....Biochemical, Genomic and Phenomic Analysis of Gastric Parietal Cells from Wildtype and Mutant Mice. The interface between the cell and its environment is the cell membrane. Signals, nutrients, and ions all have to cross this barrier. In addition, the cells contain many specialized intracellular membranous compartments. We know little about the signals that direct the synthesis of these structures and determine their final composition and shape. This grant will utilize acid secretory cells in the stomach to examine these questions because they contain a very extensive membrane system. We will use a state-of-the-art genetic and cell biological technologies to manipulate and analyse these cells in a whole animal setting.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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Gene Discovery and Functional Analysis of Copper Homeostasis Genes in Drosophila. Copper is a vital nutrient required for the formation and maintenance of bones, blood vessels and the central nervous system, but copper is also potentially toxic when in excess. Homeostatic mechanisms are needed to maintain safe levels of copper in the body and disruptions to these mechanisms are associated with disorders such as Alzheimer's disease, heart disease and osteoporosis. We are investigating the regulat ....Gene Discovery and Functional Analysis of Copper Homeostasis Genes in Drosophila. Copper is a vital nutrient required for the formation and maintenance of bones, blood vessels and the central nervous system, but copper is also potentially toxic when in excess. Homeostatic mechanisms are needed to maintain safe levels of copper in the body and disruptions to these mechanisms are associated with disorders such as Alzheimer's disease, heart disease and osteoporosis. We are investigating the regulation of a key copper pump, the Menkes protein, which helps control copper levels in the body and we are using the genetic advantages of the fruit fly Drosophila to discover new genes that regulate Menkes activity and therefore copper levels. These studies could lead to novel therapies for a range of copper-related disorders.Read moreRead less
The Molecular Basis of Copper Metabolism in Sheep. The unusual copper metabolism of sheep represents a significant agricultural problem. They are very susceptible to copper deficiency, but readily accumulate copper to toxic levels in the liver leading to fatal liver failure. We propose to elucidate the reason for the copper accumulation phenotype of sheep. We are focussing on WND, a copper transporter responsible for copper excretion into bile. We discovered a novel form of sheep WND designated ....The Molecular Basis of Copper Metabolism in Sheep. The unusual copper metabolism of sheep represents a significant agricultural problem. They are very susceptible to copper deficiency, but readily accumulate copper to toxic levels in the liver leading to fatal liver failure. We propose to elucidate the reason for the copper accumulation phenotype of sheep. We are focussing on WND, a copper transporter responsible for copper excretion into bile. We discovered a novel form of sheep WND designated WNDb to distinguish it from the normal form, WNDa. The experiments outlined are designed to understand the function of both proteins in the sheep and their role in copper sequestration.Read moreRead less
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