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
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
The Fine Tuned Physiology of Microaerophilic Gastric Spirilla. The aim of the project is to understand the molecular basis of fundamental properties of the physiology of enterogastric spiral bacteria of the genera Campylobacter and Helicobacter. The characteristics of these obligate microaerophiles which will be investigated are their aerobic respiratory chains, the special metabolites and enzymes involved in thiol-disulphide redox balance, and their essential requirement for carbon dioxide. Mic ....The Fine Tuned Physiology of Microaerophilic Gastric Spirilla. The aim of the project is to understand the molecular basis of fundamental properties of the physiology of enterogastric spiral bacteria of the genera Campylobacter and Helicobacter. The characteristics of these obligate microaerophiles which will be investigated are their aerobic respiratory chains, the special metabolites and enzymes involved in thiol-disulphide redox balance, and their essential requirement for carbon dioxide. Microaerobes include some bacteria, archea and protozoa. Realisation of the widespread habitats and importance of microaerophiles, has led recently to a vigorous interest in understanding their physiology. Knowledge of the basic properties of microaerophily has potential applications to Environmental Microbiology, Agriculture, Industrial Microbiology, Veterinary Science and Medicine.Read moreRead less
A fundamental study of the role of signal transduction pathways in the regulation of Chlamydia's complex developmental cycle. Chlamydia are unique organisms in the microbial world. They are among the smallest bacteria and yet have a complex two-stage developmental cycle. In addition they are major causes of disease in animals and humans with no vaccines available. We have used the recent flood of full genome sequence data to identify over 30 new cell signalling proteins. By understanding how the ....A fundamental study of the role of signal transduction pathways in the regulation of Chlamydia's complex developmental cycle. Chlamydia are unique organisms in the microbial world. They are among the smallest bacteria and yet have a complex two-stage developmental cycle. In addition they are major causes of disease in animals and humans with no vaccines available. We have used the recent flood of full genome sequence data to identify over 30 new cell signalling proteins. By understanding how these cell signaling proteins are organized into pathways and how this microorganism controls its complex growth and developmental cycle, we will be able to develop novel methods of control. We are at the fore front of international research and therefore uniquely placed to conduct this project.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
Brain metabolic changes in experimental malaria: a paradigm for the molecular mechanisms of intravascular inflammation. Malaria is endemic in countries directly to the north of Australia, as close as Papua New Guinea and East Timor. This project's findings about malaria also will have relevance to other infectious diseases of national importance. The outcomes will contribute to Australia's research reputation. We will build international links that will increase the national knowledge base and r ....Brain metabolic changes in experimental malaria: a paradigm for the molecular mechanisms of intravascular inflammation. Malaria is endemic in countries directly to the north of Australia, as close as Papua New Guinea and East Timor. This project's findings about malaria also will have relevance to other infectious diseases of national importance. The outcomes will contribute to Australia's research reputation. We will build international links that will increase the national knowledge base and research skill base. Young scientists will be trained in state-of-the-art research techniques in a cross-disciplinary environment that is the way of future biological research. The project may identify potential drug targets for malaria or other infectious diseases. The Intellectual Property will be protected and commercialised.Read moreRead less
The fate of single virus particles during infection. This project applies innovative imaging techniques to elucidate the logistics of cellular function. Establishing a cutting-edge technology platform will spawn discovery and research creativity in fundamental science, as well as applications in biomedical and biotechnology research disciplines. We will foster a highly skilled workforce, an essential asset for maintaining and enhancing Australia's reputation and capability as a leader in researc ....The fate of single virus particles during infection. This project applies innovative imaging techniques to elucidate the logistics of cellular function. Establishing a cutting-edge technology platform will spawn discovery and research creativity in fundamental science, as well as applications in biomedical and biotechnology research disciplines. We will foster a highly skilled workforce, an essential asset for maintaining and enhancing Australia's reputation and capability as a leader in research excellence.Read moreRead less
Host cell targets of bacterial virulence effectors. The research described in this proposal will result in a better understanding of the cell biology of host-pathogen interactions. We are in a unique position to analyze the importance of protein/protein interactions between bacterial virulence determinants and host cell proteins using a range of cell biology techniques to address the fundamental, molecular basis of the host-pathogen interaction. In addition we will construct a new genetic tool ....Host cell targets of bacterial virulence effectors. The research described in this proposal will result in a better understanding of the cell biology of host-pathogen interactions. We are in a unique position to analyze the importance of protein/protein interactions between bacterial virulence determinants and host cell proteins using a range of cell biology techniques to address the fundamental, molecular basis of the host-pathogen interaction. In addition we will construct a new genetic tool to identify novel bacterial virulence determinants. We anticipate that a greater knowledge of the factors that contribute to the host-pathogen interaction will provide new insights into the subversion of host cell processes by bacterial pathogens of animals, plants and humans.
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New inhibitors of HIV based on cellular enzymes. Over 39 million people are infected with HIV worldwide. However, none of the most highly affected countries have yet reached the peak in AIDS-related illness and death, thus the global impact of HIV/AIDS will get significantly worse, before it gets better.
In Australia, HIV is again on the rise. Ironically, improved treatments that have extended life expectancy will cause the number of HIV infected Australians to rise for many years to come. ....New inhibitors of HIV based on cellular enzymes. Over 39 million people are infected with HIV worldwide. However, none of the most highly affected countries have yet reached the peak in AIDS-related illness and death, thus the global impact of HIV/AIDS will get significantly worse, before it gets better.
In Australia, HIV is again on the rise. Ironically, improved treatments that have extended life expectancy will cause the number of HIV infected Australians to rise for many years to come. Therefore many Australians will suffer from the combined impact of the AIDS illness itself, opportunistic infections, the side-effects of treatment and natural aging. We aim to develop new drugs to combat this disease to help people everywhere lead happier, healthier and more productive lives.Read moreRead less