Modern reptiles with ancient toxins: the molecular origin and evolution of novel bioactive proteins from squamate dental glands. Animal venoms provide a rich source of novel bioactive proteins, some of which have demonstrated therapeutically useful activities. Through this researcher's unique approach of investigating previously unmapped squamate venom systems, there is potential for the identification of divergent, bioactive proteins. Those already identified by the applicant in the dental gl ....Modern reptiles with ancient toxins: the molecular origin and evolution of novel bioactive proteins from squamate dental glands. Animal venoms provide a rich source of novel bioactive proteins, some of which have demonstrated therapeutically useful activities. Through this researcher's unique approach of investigating previously unmapped squamate venom systems, there is potential for the identification of divergent, bioactive proteins. Those already identified by the applicant in the dental glands of Australian monitor lizard species represent a tremendous opportunity for biodiscovery. Further knowledge in this area will increase medical understandings of bites and aid conservation measures informed by the natural history of these animals.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
Convergent Evolution of Desert Lizards: Phylogenomic and Morphological Analyses of Limb Development. Evolutionary convergence, where similar traits evolve independently in multiple lineages, is a fundamental biological process, which affects many aspects of an organism's morphology. Despite its importance we don't understand what underlies the convergence we observe in nature - does convergence in genetic make-up underlie convergence in morphology? We will investigate whether similar hindlimb mo ....Convergent Evolution of Desert Lizards: Phylogenomic and Morphological Analyses of Limb Development. Evolutionary convergence, where similar traits evolve independently in multiple lineages, is a fundamental biological process, which affects many aspects of an organism's morphology. Despite its importance we don't understand what underlies the convergence we observe in nature - does convergence in genetic make-up underlie convergence in morphology? We will investigate whether similar hindlimb morphologies are determined by the same genetic mechanisms in iguanian lizards of Australia and North America. Our study will be the first of its kind in vertebrates and will provide significant information about the evolutionary link between an animal's morphology and its genetic make-up.Read moreRead less
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.
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
Novel mechanisms of bacterial arsenic metabolism - arsenate reduction and arsenite oxidation. Novel arsenic metabolising bacteria (i.e., arsenate respiring and arsenite oxidising), which are both phylogenetically and physiologically unique, have been isolated from arsenic-contaminated areas in Australia. The arsenate respiring bacterium, Chrysiogenes arsenatis, is of particular interest as it is the only organism reported able to respire with arsenate using the respiratory substrate acetate as t ....Novel mechanisms of bacterial arsenic metabolism - arsenate reduction and arsenite oxidation. Novel arsenic metabolising bacteria (i.e., arsenate respiring and arsenite oxidising), which are both phylogenetically and physiologically unique, have been isolated from arsenic-contaminated areas in Australia. The arsenate respiring bacterium, Chrysiogenes arsenatis, is of particular interest as it is the only organism reported able to respire with arsenate using the respiratory substrate acetate as the electron donor. It is proposed that physiological, biochemical and molecular biological studies be carried out to better understand the mechanisms by which these organisms metabolise arsenic. The knowledge gained from these studies will have worldwide application in the development of an arsenic bioremediation system.Read moreRead less
Using comparative genomics to identify genes responsible for adaptation to environmental toxins. The US National Human Genome Research Institute has committed to sequencing the genomes of ten different Drosophila (fly) species. We will search these genomes, and two others that are already available, for genes that allow flies to cope with environmental toxins found in the plants upon which they feed and breed. These same genes have the potential to degrade many of the insecticides used to con ....Using comparative genomics to identify genes responsible for adaptation to environmental toxins. The US National Human Genome Research Institute has committed to sequencing the genomes of ten different Drosophila (fly) species. We will search these genomes, and two others that are already available, for genes that allow flies to cope with environmental toxins found in the plants upon which they feed and breed. These same genes have the potential to degrade many of the insecticides used to control insect pests. Hence, this research will contribute to ongoing efforts to minimize the threat to agriculture posed by the insecticide resistance that frequently evolves in pest species. 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
Regulation of Stress Hormone Receptors in the Brain. Our research will provide information on how the brain controls our response to stress and will allow the development of targeted strategies to reduce the possibility during chronic stress of the development of conditions such as anxiety and depression. This will improve mental health outcomes in Australia and add to Australia's economic and social stability.
Characterisation of heavy metal transport genes in the plant Arabidopsis: potential roles in metal detoxification and accumulation. Plants have considerable potential for the bioremediation ("phytoremediation") of contaminated soils, including soils polluted with heavy metals. Progress has been made in understanding the physiological and biochemical mechanisms by which plants accumulate and detoxify heavy metals. One important aspect of metal detoxification is the transport of metals across cell ....Characterisation of heavy metal transport genes in the plant Arabidopsis: potential roles in metal detoxification and accumulation. Plants have considerable potential for the bioremediation ("phytoremediation") of contaminated soils, including soils polluted with heavy metals. Progress has been made in understanding the physiological and biochemical mechanisms by which plants accumulate and detoxify heavy metals. One important aspect of metal detoxification is the transport of metals across cell membranes. The recently completed genome project for the model plant Arabidopsis has identified a family of genes encoding heavy metal transport proteins. This project aims to investigate the roles of these genes in metal detoxification. In the longer term this knowledge can be applied to the improvement of phytoremediation processes.Read moreRead less