Improving the efficiency of CRISPR gene editing in cells. Human red blood cells are well-characterised and the globin gene locus is a model system for the study of gene regulation. Gene editing technologies and delivery tools are evolving rapidly and the globin gene locus is the perfect model for gene editing optimisation. This collaboration between UNSW Sydney and CSL aims to bring together our combined expertise and new technologies to develop an optimal platform for genetic modification in a ....Improving the efficiency of CRISPR gene editing in cells. Human red blood cells are well-characterised and the globin gene locus is a model system for the study of gene regulation. Gene editing technologies and delivery tools are evolving rapidly and the globin gene locus is the perfect model for gene editing optimisation. This collaboration between UNSW Sydney and CSL aims to bring together our combined expertise and new technologies to develop an optimal platform for genetic modification in a red blood cell line. Simultaneously, this project aims to generate fundamental insights into mechanisms of human gene regulation. The technological and biological outcomes of this project will be of benefit for future gene editing applications.Read moreRead less
Cellular genomic approach to the pathogenesis of multiple sclerosis. This project compares the levels of gene usage in two important immune cell types between patients with multiple sclerosis and people who do not have the disease. It aims to identify the molecular basis for the disease, in order to identify new diagnostic, preventative and treatment options.
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
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
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
Development of the PD GeneChip: a research and diagnostic tool for Parkinson's disease. The PD GeneChip will provide both social and economic benefits to Australia. It will be a key research platform for Australian scientists, and will facilitate collaboration both within Australia and overseas. It will assist with health care management of PD (Parkinson's disease) patients by providing a cost-effective diagnostic tool and the possibility of predicting the clinical course of disease. This inform ....Development of the PD GeneChip: a research and diagnostic tool for Parkinson's disease. The PD GeneChip will provide both social and economic benefits to Australia. It will be a key research platform for Australian scientists, and will facilitate collaboration both within Australia and overseas. It will assist with health care management of PD (Parkinson's disease) patients by providing a cost-effective diagnostic tool and the possibility of predicting the clinical course of disease. This information will provide the basis for tailoring treatment to a patients needs. It is anticipated that marketing of the PD GeneChip within Australia and overseas may produce revenue of at least $40 million annually.Read moreRead less
Linking mutant zebrafish phenotypes with their underlying genetic lesions. Zebrafish mutants have been generated with many interesting abnormalities, but to understand these abnormalities, the defective genes must be identified by positional cloning. We seek to identify the defective genes underpinning four mutants. Mutant #562 develops a normal nervous system which then undergoes rapid degeneration. The mutant flotte lotte has abnormal gut development. Two mutants with defective early blood for ....Linking mutant zebrafish phenotypes with their underlying genetic lesions. Zebrafish mutants have been generated with many interesting abnormalities, but to understand these abnormalities, the defective genes must be identified by positional cloning. We seek to identify the defective genes underpinning four mutants. Mutant #562 develops a normal nervous system which then undergoes rapid degeneration. The mutant flotte lotte has abnormal gut development. Two mutants with defective early blood formation will be studied. We will establish techniques for several steps that will be useful for all zebrafish mapping projects. We expect the genetic characterization of these mutants to provide new insights into nerve cell survival, gut development, and blood formation.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
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
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