A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to ....A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to explore this hypothesis and to identify the signalling molecules. We will also investigate our novel finding that a specific Ras isoform is involved in ERK5 activation. The work will provide new information on signalling pathways.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
Exploring the gene regulation networks governing mitochondrial biogenesis in Arabidopsis. Mitochondria, subcellular organelles that perform many functions indispensable to plant growth and productivity, are dynamic compartments whose protein complement changes dramatically during plant development and under stress. Yet, the cellular processes that regulate the production of these organelles are virtually unknown. By combining conventional approaches with an extremely powerful holistic method for ....Exploring the gene regulation networks governing mitochondrial biogenesis in Arabidopsis. Mitochondria, subcellular organelles that perform many functions indispensable to plant growth and productivity, are dynamic compartments whose protein complement changes dramatically during plant development and under stress. Yet, the cellular processes that regulate the production of these organelles are virtually unknown. By combining conventional approaches with an extremely powerful holistic method for simultaneously examining the expression patterns of every gene in the model plant Arabidopsis, this project will identify proteins that regulate mitochondrial biosynthesis and uncover the gene networks that these proteins control. The project outcomes will provide new opportunities for the rational manipulation of plant growth and productivity.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
Arabidopsis DNA binding proteins that control transcription of its mitochondrial genome. The increases in crop output and quality needed to drive the agricultural sector of Australia's future economy will arise from knowledge gained by combining traditional methods and the type of cutting-edge research that identifies plant mitochondrial DNA-binding proteins and their sites of action. Mitochondria are fundamental to many agronomically important traits, including plant growth, fruit ripening and ....Arabidopsis DNA binding proteins that control transcription of its mitochondrial genome. The increases in crop output and quality needed to drive the agricultural sector of Australia's future economy will arise from knowledge gained by combining traditional methods and the type of cutting-edge research that identifies plant mitochondrial DNA-binding proteins and their sites of action. Mitochondria are fundamental to many agronomically important traits, including plant growth, fruit ripening and plant stress and disease defence. Opportunities for the rational manipulation of these and hitherto undiscovered traits will come from new knowledge generated by this project, which will develop and use frontier technologies that will keep Australia at the forefront of international research into mitochondrial structure and function.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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PKC-zeta-dependent Sp1 Phosphorylation: Regulatory Insights using Novel Phospho-Specific Sp1 Antibodies and Peptide Decoys. This project will demonstrate the value of novel phospho-specific Sp1 antibodies and phospho-Sp1 peptide decoys as new molecular tools to provide invaluable insights into the regulatory roles of phosphorylated Sp1 in the control of gene expression, an area poorly defined at the present time. These agents will be used to increase our fundamental understanding of Sp1 activity ....PKC-zeta-dependent Sp1 Phosphorylation: Regulatory Insights using Novel Phospho-Specific Sp1 Antibodies and Peptide Decoys. This project will demonstrate the value of novel phospho-specific Sp1 antibodies and phospho-Sp1 peptide decoys as new molecular tools to provide invaluable insights into the regulatory roles of phosphorylated Sp1 in the control of gene expression, an area poorly defined at the present time. These agents will be used to increase our fundamental understanding of Sp1 activity by identifying physiologic agonists of the PKC-zeta-phospho-Sp1 axis and FasL-dependent apoptosis, interactions of phospho-Sp1 with the authentic FasL promoter and its recruitment of collaborative factors. The commercial exploitation of phospho-specific Sp1 antibodies and phospho-Sp1 peptide decoys will generate economic returns to Australia.Read moreRead less
Exploration of a mechanistic link between eukaryotic transcription and translation. Gene transcription is functionally coupled to other aspects of eukaryotic mRNA metabolism, emphasizing a need for integrated approaches to analyse the gene expression pathway. We have shown in previous work that yeast cells, when responding to external stimuli, show a tight correlation between changes in the transcriptome composition and homodirectional alterations in the translation state of mRNAs. This phenomen ....Exploration of a mechanistic link between eukaryotic transcription and translation. Gene transcription is functionally coupled to other aspects of eukaryotic mRNA metabolism, emphasizing a need for integrated approaches to analyse the gene expression pathway. We have shown in previous work that yeast cells, when responding to external stimuli, show a tight correlation between changes in the transcriptome composition and homodirectional alterations in the translation state of mRNAs. This phenomenon of ?potentiation? may serve to amplify signal-induced changes in the transcriptome at the translational level. This project will begin to unravel the molecular mechanisms underlying potentiation using experiments designed to distinguish between transcription- and translation-driven mechanisms.Read moreRead less