Global genetic regulation of carbon metabolism in filamentous fungi. Fungi are of great importance in medicine, agriculture and industry. They are used extensively for food, antibiotic and chemical production and, increasingly, for generating cheap substrates for bioethanol. However many are serious pathogens of plants and humans. Understanding how fungi control their metabolism is of fundamental importance for their more effective use or control. This project takes advantage of a fungus that is ....Global genetic regulation of carbon metabolism in filamentous fungi. Fungi are of great importance in medicine, agriculture and industry. They are used extensively for food, antibiotic and chemical production and, increasingly, for generating cheap substrates for bioethanol. However many are serious pathogens of plants and humans. Understanding how fungi control their metabolism is of fundamental importance for their more effective use or control. This project takes advantage of a fungus that is easily studied in the laboratory by advanced genetic techniques to identify the ways in which genes are turned on and off in response to changes in the nutrients available. By comparing DNA sequences the results are readily applied to fungi of economic importance.Read moreRead less
Molecular Genetic Analysis of Genes Regulating Metabolism in the Fungus Aspergillus nidulans. Filamentous fungi can use a wide variety of sources of carbon and nitrogen. In order to grow on these compounds metabolism is adjusted in response to changes in nutrient availability. Patterns of genome expression are altered by signalling to global regulatory genes which control the transcription of genes producing enzymes appropriate to the substrates available. This is of fundamental significance to ....Molecular Genetic Analysis of Genes Regulating Metabolism in the Fungus Aspergillus nidulans. Filamentous fungi can use a wide variety of sources of carbon and nitrogen. In order to grow on these compounds metabolism is adjusted in response to changes in nutrient availability. Patterns of genome expression are altered by signalling to global regulatory genes which control the transcription of genes producing enzymes appropriate to the substrates available. This is of fundamental significance to the physiology and development of fungi which include devastating pathogens and species used in industrial microbiology. This project aims to use the excellent molecular genetics of the model fungus Aspergillus nidulans to investigate the strategies employed and the mechanisms involved.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
Plant Genes Conferring Resistance to Ultraviolet Radiation. Ultraviolet (UV) radiation induces DNA damage that can decrease plant growth and productivity. Our aim is to begin deciphering the mechanisms responsible for the UV resistance phenotype in plants by: 1) isolating genes that control processing of UV-induced DNA damage; 2) determining the influence of UV on gene activity; and 3) elucidating the functions and essential interactions of the gene products. The results of this study will help ....Plant Genes Conferring Resistance to Ultraviolet Radiation. Ultraviolet (UV) radiation induces DNA damage that can decrease plant growth and productivity. Our aim is to begin deciphering the mechanisms responsible for the UV resistance phenotype in plants by: 1) isolating genes that control processing of UV-induced DNA damage; 2) determining the influence of UV on gene activity; and 3) elucidating the functions and essential interactions of the gene products. The results of this study will help us understand how these genes operate to produce the UV resistance phenotype. This new knowledge will facilitate eventual engineering of plants to increase agricultural productivity by enhancing resistance to solar UV radiation.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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Transcriptional and epigenetic regulation of terminal lymphocyte differentiation and alterations of the same that lead to leukemia. In the developed world infection diseases are the number three killer behind heart disease and cancer, and huge financial effort is put into treatment and prevention. Despite this, results have often been disappointing. One cause of these poor outcomes is the lack of knowledge of how effective immune responses are generated. This project aims to better understand th ....Transcriptional and epigenetic regulation of terminal lymphocyte differentiation and alterations of the same that lead to leukemia. In the developed world infection diseases are the number three killer behind heart disease and cancer, and huge financial effort is put into treatment and prevention. Despite this, results have often been disappointing. One cause of these poor outcomes is the lack of knowledge of how effective immune responses are generated. This project aims to better understand the processes that control the generation of protective lymphocytes. It will deliver information that may enable a more targeted approach to vaccine-development and treatments of infections. As defective differentiation can also be a cause of leukemia it may also lead to targets of cancer treatment.Read moreRead less
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