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
Sex, parthenogenesis and adaptation: a novel laboratory 'natural selection' experiment testing the adaptive significance of sexual and asexual reproduction. One of the greatest challenges for evolutionary biology is explaining the widespread occurrence of sexual reproduction. Many theoretical models show some inherent benefits of sex, however these models make assumptions that little or no empirical data exists for. Using a novel phenomenon found in the parasitoid wasp genus Trichogramma, I will ....Sex, parthenogenesis and adaptation: a novel laboratory 'natural selection' experiment testing the adaptive significance of sexual and asexual reproduction. One of the greatest challenges for evolutionary biology is explaining the widespread occurrence of sexual reproduction. Many theoretical models show some inherent benefits of sex, however these models make assumptions that little or no empirical data exists for. Using a novel phenomenon found in the parasitoid wasp genus Trichogramma, I will investigate the adaptive significance of sexual and asexual reproduction in a laboratory natural selection experiment and therefore directly test the theory for the evolution and maintenance of sex. This will be the first such test in a higher organism.Read moreRead less
The Evolution and Diversification of Apicomplexan Cell Invasion Mechanisms. Insights gained through this project, about the mechanisms of cell invasion in Apicomplexan parasites, will have far reaching implications for a number of parasites of great significance to humans and animals. Since host cell invasion is a key step in the parasite lifecycle, proteins identified here will be prime targets for novel drugs that prevent invasion or antigens that can be used as vaccines. This will be importan ....The Evolution and Diversification of Apicomplexan Cell Invasion Mechanisms. Insights gained through this project, about the mechanisms of cell invasion in Apicomplexan parasites, will have far reaching implications for a number of parasites of great significance to humans and animals. Since host cell invasion is a key step in the parasite lifecycle, proteins identified here will be prime targets for novel drugs that prevent invasion or antigens that can be used as vaccines. This will be important for developing new control strategies for diseases of global significance such as malaria or toxoplasmosis, as well as those of national importance to the food industry of Australia, including diseases like babesiosis and coccidiosis that cause significant economic loss to the livestock and poultry industries each year.Read moreRead less
Dissecting insect gut function to understand insecticide detoxification. Massive quantities of chemical insecticides are used daily to control the insect pests that threaten agriculture, human health and the welfare of domestic pets. Insects readily evolve resistance to these chemicals reducing the effectiveness of pest control, increasing the amount of chemical used and increasing costs to consumers. This project examines the way in which insects adapt to the extreme stress imposed on them by ....Dissecting insect gut function to understand insecticide detoxification. Massive quantities of chemical insecticides are used daily to control the insect pests that threaten agriculture, human health and the welfare of domestic pets. Insects readily evolve resistance to these chemicals reducing the effectiveness of pest control, increasing the amount of chemical used and increasing costs to consumers. This project examines the way in which insects adapt to the extreme stress imposed on them by chemical insecticides. A thorough understanding of this adaptation process is required before insecticide resistance can be effectively managed or prevented. Read moreRead less
Fish venom as a model system for the molecular evolution of defensive toxins. The key aim of this study is to undertake a thorough investigation of venoms found in distinct fish lineages, including enigmatic species such as venomous and medically important species such as the stonefish. By characterising the biodiversity of toxins found in the venoms of different fish, the evolutionary history of venom in this major vertebrate lineage can be revealed. The investigations proposed here will also d ....Fish venom as a model system for the molecular evolution of defensive toxins. The key aim of this study is to undertake a thorough investigation of venoms found in distinct fish lineages, including enigmatic species such as venomous and medically important species such as the stonefish. By characterising the biodiversity of toxins found in the venoms of different fish, the evolutionary history of venom in this major vertebrate lineage can be revealed. The investigations proposed here will also determine the functional activities of different venoms and their components. This will not only help the understanding of the medical consequences of the annual thousands of fish envenomings but also explore a largely unstudied resource for the discovery of new pharmacological diagnostics and therapeutics.Read moreRead less
Characterising a new regulator of the Hedgehog pathway . The Hedgehog pathway is crucial for embryonic development, and disruption causes multi-organ morphogenesis defects. The CI team has uncovered a new gene required for Hedgehog signalling in mouse, zebrafish, and Drosophila. Preliminary data hints at mechanism for this novel gene and shows it may in fact be a member of a new superfamily. The project will examine gene function and identify interacting protein partners, using the zebrafish, Dr ....Characterising a new regulator of the Hedgehog pathway . The Hedgehog pathway is crucial for embryonic development, and disruption causes multi-organ morphogenesis defects. The CI team has uncovered a new gene required for Hedgehog signalling in mouse, zebrafish, and Drosophila. Preliminary data hints at mechanism for this novel gene and shows it may in fact be a member of a new superfamily. The project will examine gene function and identify interacting protein partners, using the zebrafish, Drosophila, and cell-based models. Findings will provide basic knowledge about this mysterious gene and uncover how it modulates an essential pathway in embryonic development. This research is expected to impact knowledge generation, health, and well-being.Read moreRead less
Evolutionary venomics: Venom system diversification in the animal kingdom. This proposal represents a tremendous opportunity for biodiscovery from the Australian toxic fauna. This will be achieved through the researcher's unique approach of investigating previously unmapped venom systems for divergent, bioactive proteins. An understanding of venomous animal protein evolution has practical implications for the treatment of envenomations - an enormous problem in Australia - as well as great pot ....Evolutionary venomics: Venom system diversification in the animal kingdom. This proposal represents a tremendous opportunity for biodiscovery from the Australian toxic fauna. This will be achieved through the researcher's unique approach of investigating previously unmapped venom systems for divergent, bioactive proteins. An understanding of venomous animal protein evolution has practical implications for the treatment of envenomations - an enormous problem in Australia - as well as great potential in drug discovery and other commercial applications. This project will provide Australian graduate and post-graduate students with finely tuned skills in cutting edge methodological techniques and a fluent understanding of molecular evolution, preparing them to be internationally competitive scientists.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
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
Molecular evolution and toxinology of colubrid snake venom toxins. This project proposes to examine the origin and evolution of venom systems in advanced snakes (Caenophidia) focusing on the colubrid radiation comprising the rear-fanged species. Demonstration by us of the presence of a potent postsynaptic neurotoxin in the Durvenoy's secretions of the Asian ratsnake Elaphe radiata, an archetypal non-venomous colubrid species, forced a fundamental rethink of venom evolution. The toxin is homologo ....Molecular evolution and toxinology of colubrid snake venom toxins. This project proposes to examine the origin and evolution of venom systems in advanced snakes (Caenophidia) focusing on the colubrid radiation comprising the rear-fanged species. Demonstration by us of the presence of a potent postsynaptic neurotoxin in the Durvenoy's secretions of the Asian ratsnake Elaphe radiata, an archetypal non-venomous colubrid species, forced a fundamental rethink of venom evolution. The toxin is homologous with the three finger toxins, previously thought unique to elapids, and supports the role of venom as a key evolutionary innovation in the diversification of advanced snakes. This project extends this work to other species and toxin families.Read moreRead less