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
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
Breaking selective constraints: is Hsp90 a capacitor of evolutionary change? Gene action and expression can be modulated by genetic mechanisms. If a general mechanism controlling gene expression exists that can be easily manipulated it has the potential to allow animal and plant breeders to quickly produce and select for new characters of agricultural importance without relying on transgenics and long-term breeding programs. It would also assist in the development of tools for identifying and de ....Breaking selective constraints: is Hsp90 a capacitor of evolutionary change? Gene action and expression can be modulated by genetic mechanisms. If a general mechanism controlling gene expression exists that can be easily manipulated it has the potential to allow animal and plant breeders to quickly produce and select for new characters of agricultural importance without relying on transgenics and long-term breeding programs. It would also assist in the development of tools for identifying and detecting genes that increase susceptibility to human diseases, such as cancer, that are only expressed under certain conditions environmental. I intend to determine whether the protein Hsp90 represents a general mechanism controlling gene expression. Read moreRead less
Further Genetic and Molecular studies of an Important Prokaryotic Regulator Protein TyrR. Genomes encode many functions whose expression varies dramatically depending on particular cellular environments. Special proteins called Regulator Proteins act as sensors to detect subtle changes in the environment and, in response, to influence the expression of certain genes either dampening them down or stimulating their activity. We are working with the TyrR regulator protein of the simple bacterium E ....Further Genetic and Molecular studies of an Important Prokaryotic Regulator Protein TyrR. Genomes encode many functions whose expression varies dramatically depending on particular cellular environments. Special proteins called Regulator Proteins act as sensors to detect subtle changes in the environment and, in response, to influence the expression of certain genes either dampening them down or stimulating their activity. We are working with the TyrR regulator protein of the simple bacterium Escherichia coli to elucidate the molecular strategies used in these controls. Because this protein controls the expression of a number of genes with diverse functions, evolution has selected equally diverse mechanisms to achieve appropriate transcriptional responses. The detailed knowledge of the E.coli genome and of the various genes regulated by TyrR make it an excellent system for such fundamental studies.Read moreRead less
Mechanisms of zinc transport and homeostasis in plants. Zinc deficiency is a widespread factor limiting crop production and affects many soils of southern Australia and around the world. Genetic techniques can be used to identify zinc-efficient crop breeds able to grow well under zinc deficient conditions and able to efficiently deliver zinc to cereal grains to alleviate nutritional zinc-deficiency in humans. This project will identify new genes important in zinc transport and homeostasis in pla ....Mechanisms of zinc transport and homeostasis in plants. Zinc deficiency is a widespread factor limiting crop production and affects many soils of southern Australia and around the world. Genetic techniques can be used to identify zinc-efficient crop breeds able to grow well under zinc deficient conditions and able to efficiently deliver zinc to cereal grains to alleviate nutritional zinc-deficiency in humans. This project will identify new genes important in zinc transport and homeostasis in plants and will ultimately allow their role in zinc efficient crops to be assessed. This will contribute to more rapid and directed strategies in breeding zinc efficient crops.Read moreRead less
Testing the DNA decay hypothesis of ecological specialization. Australia's biodiversity has been increasingly threatened by climate change and fragmentation from habitat loss. To conserve biodiversity we need to identify species most at risk of extinction. One way species avoid extinction is to evolve and adapt to changing conditions, however, it now appears that many species have a limited adaptive potential. Here we develop and test a new idea that helps to predict species most threatened b ....Testing the DNA decay hypothesis of ecological specialization. Australia's biodiversity has been increasingly threatened by climate change and fragmentation from habitat loss. To conserve biodiversity we need to identify species most at risk of extinction. One way species avoid extinction is to evolve and adapt to changing conditions, however, it now appears that many species have a limited adaptive potential. Here we develop and test a new idea that helps to predict species most threatened by climate change and other types of stresses. We also identify the sets of genes that are involved in adapting to dry/cold conditions and toxins. This information provides a rapid way of identifying species most at risk and least likely to adapt, and a new perspective on Australia's biodiversity.Read moreRead less
Genetic association studies of fundamental wood fibre components in Pinus radiata resource populations. Radiata pine is Australia's premiere softwood plantation species occupying in excess of one million hectares, contributing over $18 billion to Australia's GNP and providing employment to 130,000 Australians. With a trade deficit in forest and forest products of $1.85 billion, current massive plantation establishment efforts are in train to reverse this trend. These have to be backed by researc ....Genetic association studies of fundamental wood fibre components in Pinus radiata resource populations. Radiata pine is Australia's premiere softwood plantation species occupying in excess of one million hectares, contributing over $18 billion to Australia's GNP and providing employment to 130,000 Australians. With a trade deficit in forest and forest products of $1.85 billion, current massive plantation establishment efforts are in train to reverse this trend. These have to be backed by research into the factors that determine the base resource's quality, growth and sustainability. Results will lead to improved resource quality, increased productivity and new industrial opportunities, directly improving our trade position and releasing pressure on our native forest resources.Read moreRead less
A high-through-put method for unlocking the mitochondrial genomes of significant pathogens. The national/community benefits of this research are: (1) to develop a long-term, high quality scientific and technological program contributing to national objectives, including the maintenance of a strong capability in basic research, the development of new scientific concepts and the enhancement of international collaborative links; (2) to strengthen the links between basic and applied research; (3) to ....A high-through-put method for unlocking the mitochondrial genomes of significant pathogens. The national/community benefits of this research are: (1) to develop a long-term, high quality scientific and technological program contributing to national objectives, including the maintenance of a strong capability in basic research, the development of new scientific concepts and the enhancement of international collaborative links; (2) to strengthen the links between basic and applied research; (3) to develop excellence in research by promoting collaborative research, resulting in a more efficient use of resources in a national and international context; (4) to enhance the skills-base in biology and biotechnology; and (5) to substantially increase global visibility through quality research, leading to an increased investment in Australian science.Read moreRead less