New models of mitochondrial fatty acid oxidation disorders. Mitochondrial disease can affect both children and adults and is often fatal. This project will study mitochondrial function in cell types of the heart and brain to better understand how they generate energy in these tissues. This will provide new insights into mitochondrial metabolism and how defects in this process cause mitochondrial disease.
Characterization of metabolic networks in a microbial pathogen. New methods are needed to understand complex cellular processes such as metabolism. This proposal will support the development of methods in metabolite profiling and flux analysis that provide a global view of metabolic networks in cells and complement other profiling approaches, such as proteomics and transcriptomics. The development of these approaches (collectively termed Systems Biology) is essential for maintaining Australia sc ....Characterization of metabolic networks in a microbial pathogen. New methods are needed to understand complex cellular processes such as metabolism. This proposal will support the development of methods in metabolite profiling and flux analysis that provide a global view of metabolic networks in cells and complement other profiling approaches, such as proteomics and transcriptomics. The development of these approaches (collectively termed Systems Biology) is essential for maintaining Australia science at the forefront of international efforts (National Research Priority 3; Breakthrough science). This project will also directly contribute to our understanding of metabolism of an important human pathogen and provide training to young Australian scientists.Read moreRead less
Investigation of a Novel Protein Implicated in Phosphate Metabolism in Bacteria. Phosphate is an important nutrient for all forms of life on Earth. A novel bacterial protein has been identified that appears to be important for the uptake or processing of phosphate, since mutants lacking the protein grow poorly inside certain cells of the human immune system (where phosphate levels are low) and in media containing low phosphate. The aims of this project are: to determine the role of the protein b ....Investigation of a Novel Protein Implicated in Phosphate Metabolism in Bacteria. Phosphate is an important nutrient for all forms of life on Earth. A novel bacterial protein has been identified that appears to be important for the uptake or processing of phosphate, since mutants lacking the protein grow poorly inside certain cells of the human immune system (where phosphate levels are low) and in media containing low phosphate. The aims of this project are: to determine the role of the protein by examining all phosphate containing molecules in our mutants; to determine its location in bacteria and functional domains; to identify other affected genes in our mutants; and, to find proteins that interact with this new protein. This project expects to demonstrate the importance of this protein in phosphate metabolism in bacteria.Read moreRead less
Transfer ribonucleic acid (tRNA) synthetases as drug targets in Plasmodium falciparum. Malaria is a major worldwide infectious disease. The disease kills around 2 million people every year, and current drugs are increasingly failing due to parasite drug resistance, creating an urgent demand for new drugs, that inhibit different targets. The Fellow will study a new class of parasite drug targets, the transfer ribonucleic acid (tRNA) synthetase enzymes to find novel inhibitors. Compounds blocking ....Transfer ribonucleic acid (tRNA) synthetases as drug targets in Plasmodium falciparum. Malaria is a major worldwide infectious disease. The disease kills around 2 million people every year, and current drugs are increasingly failing due to parasite drug resistance, creating an urgent demand for new drugs, that inhibit different targets. The Fellow will study a new class of parasite drug targets, the transfer ribonucleic acid (tRNA) synthetase enzymes to find novel inhibitors. Compounds blocking these enzymes may lead to new drugs to combat malaria.Read moreRead less
Mannosyl transfer processes in leishmania and mycobacteria. The human diseases leishmaniasis and tuberculosis are caused by infectious microorganisms. We will target pathways to the biosynthesis and degradation of parasite-specific mannose containing metabolites that play essential roles in the ability of these pathogens to cause disease. We will develop new ways to study these pathways, and will synthesize novel substrates and inhibitors that will allow the development of antituberculosis and a ....Mannosyl transfer processes in leishmania and mycobacteria. The human diseases leishmaniasis and tuberculosis are caused by infectious microorganisms. We will target pathways to the biosynthesis and degradation of parasite-specific mannose containing metabolites that play essential roles in the ability of these pathogens to cause disease. We will develop new ways to study these pathways, and will synthesize novel substrates and inhibitors that will allow the development of antituberculosis and antileishmanial drugs. This project will contribute to our national competitiveness in the newly emerging area of chemical biology.Read moreRead less
Mannose metabolism in pathogenic microorganisms. Current treatments for tuberculosis and leishmaniasis are failing due to chronic underinvestment by the private sector and public agencies over many decades. The causative agents, the microorganisms Leishmania spp and Mycobacterium tuberculosis, respectively, use sugar processing pathways that differ from humans, and thus represent targets for new drugs. We will study two related sugar-processing biochemical pathways in these organisms. We will de ....Mannose metabolism in pathogenic microorganisms. Current treatments for tuberculosis and leishmaniasis are failing due to chronic underinvestment by the private sector and public agencies over many decades. The causative agents, the microorganisms Leishmania spp and Mycobacterium tuberculosis, respectively, use sugar processing pathways that differ from humans, and thus represent targets for new drugs. We will study two related sugar-processing biochemical pathways in these organisms. We will develop new ways to measure enzyme activity using mass spectrometry, and new reagents to clone several biosynthetic enzymes. Our work will lay a foundation for new antibiotics to combat these insidious diseases, and will foster Australian expertise in chemical biology and innovative basic science.Read moreRead less
Discovery and development of novel insulin sensitising compounds for the treatment of Type 2 diabetes. Diabetes is one of the major health problems facing Australia today, and current treatments are proving inadequate to combat this disease. We previously discovered a new drug with potential for development for the treatment of diabetes. In this project, we will identify how this drug works to combat diabetes in cell and animal models, and use novel chemistry approaches to modify the drug to imp ....Discovery and development of novel insulin sensitising compounds for the treatment of Type 2 diabetes. Diabetes is one of the major health problems facing Australia today, and current treatments are proving inadequate to combat this disease. We previously discovered a new drug with potential for development for the treatment of diabetes. In this project, we will identify how this drug works to combat diabetes in cell and animal models, and use novel chemistry approaches to modify the drug to improve its properties and reduce potential side-effects. The outcomes of this project will be understanding of a new biological process that contributes to the development of diabetes, and the discovery and characterisation of new chemical compounds that could be developed as drugs to treat diabetes.Read moreRead less
Cytopathological roles of AMPK in mitochondrial dysfunction. This research project will benefit the Australian community by deepening our understanding of mitochondrial and neurodegenerative diseases. These diseases are incurable and treatment options are limited. The knowledge gained in this project should assist in the development of new or improved treatments. The project will also contribute to the training of young scientists in biomedical research and will enhance Australia's international ....Cytopathological roles of AMPK in mitochondrial dysfunction. This research project will benefit the Australian community by deepening our understanding of mitochondrial and neurodegenerative diseases. These diseases are incurable and treatment options are limited. The knowledge gained in this project should assist in the development of new or improved treatments. The project will also contribute to the training of young scientists in biomedical research and will enhance Australia's international scientific reputation because it involves a significant and novel biomedical discovery.
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Metabolic Profiling of Human Embryonic Stem Cells. Stem cell therapies are becoming a commercial reality. Stem cell products have an estimated value of US$ 87 million this year and are predicted to be worth US$ 8.5 billion within a decade. Development of stem cell products will be an international research effort with many contributing to the final products. Research described here will augment this effort, strengthening Australia's contribution by developing novel intellectual property and appl ....Metabolic Profiling of Human Embryonic Stem Cells. Stem cell therapies are becoming a commercial reality. Stem cell products have an estimated value of US$ 87 million this year and are predicted to be worth US$ 8.5 billion within a decade. Development of stem cell products will be an international research effort with many contributing to the final products. Research described here will augment this effort, strengthening Australia's contribution by developing novel intellectual property and applications. The training of individuals skilled in stem cell research will add to Australia's pool of stem cell researchers. Individuals trained in this area will be paramount to maintaining Australia's research effort and in the application of these technologies into the Australian health sector.Read moreRead less
Use of a cell based assay to identify novel insulin-sensitising agents. Diabetes and obesity are currently escalating to epidemic proportions in Australia and there is an urgent need to develop new therapeutics. A major feature of these disorders is impaired insulin action. We have recently developed and validated an exciting new assay for insulin action in fat cells. In this project we propose an exciting research program encompassing major research and biotechnology groups in Australia to u ....Use of a cell based assay to identify novel insulin-sensitising agents. Diabetes and obesity are currently escalating to epidemic proportions in Australia and there is an urgent need to develop new therapeutics. A major feature of these disorders is impaired insulin action. We have recently developed and validated an exciting new assay for insulin action in fat cells. In this project we propose an exciting research program encompassing major research and biotechnology groups in Australia to utilise this technology to identify novel insulin-sensitising agents. These agents will be used for drug discovery purposes by our industry partner ChemGenex and as novel tools to dissect the mechanism of insulin action.Read moreRead less