Structure and function of a new class of multi-zinc finger (MZF) transcriptional regulators. An understanding of how genes are switched on and off during the development and lifetime of an organism is central to developing the ability to fight many diseases in a rational way. This project will advance our knowledge in this area at a fundamental molecular level by examining the mechanisms through which a specific set of proteins controls gene expression.
Adaptive Evolution of BRCA1 in Ancestral Mammals. This project investigates adaptive evolution of BRCA1 in the early radiation of mammals. We will test the hypothesis that the evolution of mammary glands and X chromosome inactivation has resulted in modification of the BRCA1 protein sequence as it aquired new roles in these processes. We will also investigate the importance of these changes inducing compensatory changes in other parts of the protein.
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
Identifying genes causing thermal evolution of ectotherm body size. Cold-blooded animals increase in body size as they are found in populations at greater distances from the equator. These patterns are due to populations adapting to temperature. The aim of this project is to identify the genes involved in this adaptation process. We will do this by taking advantage of a well-studied body size cline in the vinegar fly on the east coast of Australia, and by building on an international collaborati ....Identifying genes causing thermal evolution of ectotherm body size. Cold-blooded animals increase in body size as they are found in populations at greater distances from the equator. These patterns are due to populations adapting to temperature. The aim of this project is to identify the genes involved in this adaptation process. We will do this by taking advantage of a well-studied body size cline in the vinegar fly on the east coast of Australia, and by building on an international collaboration between a leading UK and two Australian research groups. In doing so we will provide an explanation at the molecular level for one of the great unresolved phenomena in biology: why do cold-blooded animals get bigger in the cold? The research also leads to the potential to manipulate body size in animals.Read moreRead less
A Genomic Dissection of Natural Adaptation in Mate Recognition. Adaptation is a fundamental area of evolutionary biology but we know surprisingly little about its underlying genetic basis. As a process, adaptation poses several challenges for Australian society including bacterial evolution of resistance to antibiotics, HIV resistance to antiviral medications and the evolution of pesticide resistance in agricultural pests. This study will use a model system and genomic tools to test theoretical ....A Genomic Dissection of Natural Adaptation in Mate Recognition. Adaptation is a fundamental area of evolutionary biology but we know surprisingly little about its underlying genetic basis. As a process, adaptation poses several challenges for Australian society including bacterial evolution of resistance to antibiotics, HIV resistance to antiviral medications and the evolution of pesticide resistance in agricultural pests. This study will use a model system and genomic tools to test theoretical models of the genetic basis of adaptation. This integrative approach will enhance Australia's research profile in genomics and evolutionary biology. The project will provide emerging scientists with skills in areas including genomics, molecular biology, evolutionary biology and agricultural genetics.Read moreRead less
Maximising knowledge from dense SNP (single nucleotide polymorphisms) data using multi-locus analysis. The genomics revolution has made it possible to measure thousands of DNA variants in individuals. This information can be used in many ways, including to find genes that cause variation between individuals in a population and to estimate the size of the population in the past. Our study will lead an analysis method that will extract more information out of such data. This will improve the effi ....Maximising knowledge from dense SNP (single nucleotide polymorphisms) data using multi-locus analysis. The genomics revolution has made it possible to measure thousands of DNA variants in individuals. This information can be used in many ways, including to find genes that cause variation between individuals in a population and to estimate the size of the population in the past. Our study will lead an analysis method that will extract more information out of such data. This will improve the efficiency of gene mapping methods, including applications in humans for traits related to productive ageing and a healthy start to life, will allow the estimation of genetic relatedness and genetic variation in natural populations, and will lead to more efficient selection programs in agricultural populations.Read moreRead less
Genetic manipulation of Clostridium sporogenes. The overall objective of this project is to develop genetic methods for the manipulation of the anaerobic bacterium Clostridium sporogenes. Specifically, the project aims to manipulate this microorganism so that genes encoding enzymes that convert prodrugs to anticancer drugs can be introduced and stably maintained on its chromosome. The significance of the project is that the resultant bacteria, and others constructed using these methods, will th ....Genetic manipulation of Clostridium sporogenes. The overall objective of this project is to develop genetic methods for the manipulation of the anaerobic bacterium Clostridium sporogenes. Specifically, the project aims to manipulate this microorganism so that genes encoding enzymes that convert prodrugs to anticancer drugs can be introduced and stably maintained on its chromosome. The significance of the project is that the resultant bacteria, and others constructed using these methods, will then be able to be tested for their ability to act as specific drug delivery systems for use in the treatment of solid tumours.Read moreRead less
Origin of multicellularity in animals: identification and analysis of intercellular signalling pathways in a basal metazoan, the demosponge Reniera. The Reniera genome project is a multi-million dollar collaboration between JGI (US-DOE) and Australian scientists that will see the sequencing of the first Australian marine animal by 2006. This project will significantly advance our understanding of the origins of animals and contribute to the reconstruction of creatures that lived over 600 million ....Origin of multicellularity in animals: identification and analysis of intercellular signalling pathways in a basal metazoan, the demosponge Reniera. The Reniera genome project is a multi-million dollar collaboration between JGI (US-DOE) and Australian scientists that will see the sequencing of the first Australian marine animal by 2006. This project will significantly advance our understanding of the origins of animals and contribute to the reconstruction of creatures that lived over 600 million years ago. A major outcome of this reconstruction will be a fundamental understanding of how cells communicate with each other during the process of development to give rise to the diversity of cell types within multicellular animals. This study will also shed light on what happens when cell communication goes astray, as observed in a range of human malignancies, including cancer. Read moreRead less
Co-ordinated Action of ATM and DNA-PK in DNA damage recognition. The aim of this project is to investigate the mechanism of repair of double straind breaks in DNA sustained after radiation damage. Specifically we will focus on two proteins ATM (mutated in the genetic disorder ataxia-telangiectasia) and DNA-PK mutated in scid mice. There two proteins recognize double straind breaks in DNA and signal this damage to the DNA repair machinery of the cell and to cell cycle checkpoints. The emphasis ....Co-ordinated Action of ATM and DNA-PK in DNA damage recognition. The aim of this project is to investigate the mechanism of repair of double straind breaks in DNA sustained after radiation damage. Specifically we will focus on two proteins ATM (mutated in the genetic disorder ataxia-telangiectasia) and DNA-PK mutated in scid mice. There two proteins recognize double straind breaks in DNA and signal this damage to the DNA repair machinery of the cell and to cell cycle checkpoints. The emphasis here will be in the relationship between the two proteins in co-ordinating the repair of breaks in DNA. This information will be important in understanding mechanisms for maintaining the integrity of the genome.Read moreRead less
Drosophila Quantitative Genomics. This research proposal will be a key element in the emerging program in evolutionary and ecological functional genomics at the University of Queensland. Our studies utilize modern genomics approaches to address diverse national priorities from conservation of biological resources in the face of climate change, to understanding how genetic history contributes to drug susceptibility. The research will contribute to the intellectual foundation upon which rigorous ....Drosophila Quantitative Genomics. This research proposal will be a key element in the emerging program in evolutionary and ecological functional genomics at the University of Queensland. Our studies utilize modern genomics approaches to address diverse national priorities from conservation of biological resources in the face of climate change, to understanding how genetic history contributes to drug susceptibility. The research will contribute to the intellectual foundation upon which rigorous environmental and biomedical research is built. Social impact will be seen in the training of a new generation of integrative genome biologists, and the shaping of attitudes toward the role of genetics in human biology.Read moreRead less