Exploitation of a Novel Drug Target for Controlling Animal Trypanosomiasis. Trypanosomiasis greatly reduces livestock productivity in countries where it is endemic and is a threat to livestock and native wildlife in countries such as Australia where it is exotic but there is a risk of entry. New trypanocidal drugs with different modes of action are urgently needed to overcome growing resistance. This project aims to characterise trypanosome tubulin and, with this information, produce new tubulin ....Exploitation of a Novel Drug Target for Controlling Animal Trypanosomiasis. Trypanosomiasis greatly reduces livestock productivity in countries where it is endemic and is a threat to livestock and native wildlife in countries such as Australia where it is exotic but there is a risk of entry. New trypanocidal drugs with different modes of action are urgently needed to overcome growing resistance. This project aims to characterise trypanosome tubulin and, with this information, produce new tubulin-binding compounds for assessment in vitro and in vivo. Upon completion of the project it is expected that drug binding sites on trypanosome tubulin will be characterised and at least one candidate for clinical trials identified.Read moreRead less
The host specificity of bacterial pathogens. The vast majority of microorganisms that cause diseases in animals are host specific. In other words, they cause disease exclusively in a particular animal species, but are harmless for others. Despite considerable recent advances in our understanding of the mechanisms used by microorganisms in general to cause disease, in most cases the underlying basis of host-specificity is not known. In this project, we will use two animal pathogens, rabbit-spe ....The host specificity of bacterial pathogens. The vast majority of microorganisms that cause diseases in animals are host specific. In other words, they cause disease exclusively in a particular animal species, but are harmless for others. Despite considerable recent advances in our understanding of the mechanisms used by microorganisms in general to cause disease, in most cases the underlying basis of host-specificity is not known. In this project, we will use two animal pathogens, rabbit-specific enteropathogenic E. coli and the closely related bacterium, Citrobacter rodentium, which specifically infect rabbits and mice respectively, to investigate the molecular basis of host specificity.Read moreRead less
Toward novel approaches for the control of parasitic nematodes via genomics/phenomics. The control of economically important parasitic worms of livestock relies heavily on the use of chemical compounds (anthelmintics). Their excessive and uncontrolled use has led to serious anthelmintic resistance problems in parasites, so that many treatments are no longer effective, and also to residue problems in meat, milk and the environment. We will use 'cutting edge' technologies to provide unique insight ....Toward novel approaches for the control of parasitic nematodes via genomics/phenomics. The control of economically important parasitic worms of livestock relies heavily on the use of chemical compounds (anthelmintics). Their excessive and uncontrolled use has led to serious anthelmintic resistance problems in parasites, so that many treatments are no longer effective, and also to residue problems in meat, milk and the environment. We will use 'cutting edge' technologies to provide unique insights into the molecular processes of parasite growth and reproduction, to develop safe and sustainable intervention strategies for parasites. The project will provide a unique technology platform and a skills base in parasite genomics and will generate significant intellectual property.Read moreRead less
Elucidating a key developmental switch in Haemonchus contortus using a massively parallel picolitre reactor sequencing-coupled genomic and bioinformatic platform. The national/community benefits of this project include enhanced focus on animal and human health biotechnology through the development of safe anti-parasite compounds/vaccines; improved and sustainable control of key parasites with decreased risk of induction of drug resistance; increased profitability of agricultural animal productio ....Elucidating a key developmental switch in Haemonchus contortus using a massively parallel picolitre reactor sequencing-coupled genomic and bioinformatic platform. The national/community benefits of this project include enhanced focus on animal and human health biotechnology through the development of safe anti-parasite compounds/vaccines; improved and sustainable control of key parasites with decreased risk of induction of drug resistance; increased profitability of agricultural animal production; consolidation of a technology platform for further applications in genomics and post-genomics of pathogens of global significance and construction of a pipeline for the validation of drug targets; capturing the benefits from fundamental research and strengthening links between fundamental and applied research; and increasing the quality and quantity of scientifically skilled people in biotechnology.Read moreRead less
Discovery of early developmental events in the transition to parasitism in the hookworm Ancylostoma caninum using genomic technologies. The national/community benefits 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 a ....Discovery of early developmental events in the transition to parasitism in the hookworm Ancylostoma caninum using genomic technologies. The national/community benefits 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; (5) to substantially increase global visibility through quality research, leading to an increased investment in Australian science.Read moreRead less
Identifying Novel Biosynthetic Pathways in Mycobacteria using DNA Microarray Technology. DNA microarrays are a powerful new bioinformatics-based technology and an ideal tool for characterising complex biosynthetic pathways since the expression of all genes in the bacterial genome can be monitored in a single experiment. In this project we aim to construct and use a DNA microarray to identify novel biosynthetic pathways in mycobacteria. Of particular interest are pathways used to create compone ....Identifying Novel Biosynthetic Pathways in Mycobacteria using DNA Microarray Technology. DNA microarrays are a powerful new bioinformatics-based technology and an ideal tool for characterising complex biosynthetic pathways since the expression of all genes in the bacterial genome can be monitored in a single experiment. In this project we aim to construct and use a DNA microarray to identify novel biosynthetic pathways in mycobacteria. Of particular interest are pathways used to create components of the highly complex and poorly characterised cell wall. Since this structure is unique in the bacterial world, we expect to identify and characterise pathways that are unique to mycobacteria.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
Cultivating numerically significant soil bacteria. The vast majority of soil bacteria have not been able to be studied in the laboratory because they cannot be grown outside the soil. They are therefore termed unculturable. Most of these belong to groups that are completely unstudied. Advances made in the Janssen lab have overcome this impediment to laboratory cultivation of numerically abundant and globally distributed soil bacteria. This project will develop these advances to generate simple a ....Cultivating numerically significant soil bacteria. The vast majority of soil bacteria have not been able to be studied in the laboratory because they cannot be grown outside the soil. They are therefore termed unculturable. Most of these belong to groups that are completely unstudied. Advances made in the Janssen lab have overcome this impediment to laboratory cultivation of numerically abundant and globally distributed soil bacteria. This project will develop these advances to generate simple and widely applicable methods to enable many of the previously unculturable soil bacteria to be studied. This will allow assessments of their ecological roles and biotechnological potentials to be made.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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Disulfide catalysis and protein folding in bacterial virulence. The molecular mechanisms that underpin disulfide bond formation have had a major impact on our understanding of protein folding and function. This project will make a major contribution to fundamental areas of disulfide catalysis pathways in bacterial pathogens and thus help maintain a strong international profile for Australian research in this field. The work will lead to training of research scientists and students in techniques ....Disulfide catalysis and protein folding in bacterial virulence. The molecular mechanisms that underpin disulfide bond formation have had a major impact on our understanding of protein folding and function. This project will make a major contribution to fundamental areas of disulfide catalysis pathways in bacterial pathogens and thus help maintain a strong international profile for Australian research in this field. The work will lead to training of research scientists and students in techniques that include molecular genetics, protein biochemistry and structural biology. Our findings may impact future directions for vaccine research on pathogens that cause life threatening infections in humans and therefore lead to improved health and reduced health care expenditure.Read moreRead less