Phase-variable epigenetic regulators in bacterial veterinary pathogens. This project aims to identify phasevarion regulated genes in the major bacterial swine pathogens Streptococcus suis and Actinobacillus pleuropneumoniae. Both species contain randomly switching epigenetic regulators that control expression of multiple genes by epigenetic mechanisms. Identifying phasevarion controlled genes will inform and direct future vaccine development for important livestock species.
Defining the molecular basis for Salmonella persistence. Salmonella infections in animals and humans place significant burdens on the agri-food and healthcare sectors. All mammals and avian species can become chronically infected with Salmonella and such chronic carriage is a reservoir for disease and outbreaks in other animals and humans. Significant gaps in our understanding of Salmonella infection remain, including the molecular mechanisms involved in establishing a chronic carrier state. We ....Defining the molecular basis for Salmonella persistence. Salmonella infections in animals and humans place significant burdens on the agri-food and healthcare sectors. All mammals and avian species can become chronically infected with Salmonella and such chronic carriage is a reservoir for disease and outbreaks in other animals and humans. Significant gaps in our understanding of Salmonella infection remain, including the molecular mechanisms involved in establishing a chronic carrier state. We identified several Salmonella specific genes and subsequent murine studies revealed that a Salmonella mutant lacking these genes is attenuated in mice and especially in the gallbladder. In this project we seek to understand the molecular basis for attenuation and the contribution of each protein to diseaseRead moreRead less
Understanding the origin, epidemiology and transmission threat of chlamydial infections between Australian native animals and livestock. Chlamydial infections of koalas and livestock cause diseases of significant economic and environmental concern. Molecular analysis of livestock and native animal strains will improve understanding of the factors associated with transmission of these important pathogens, improving the ability to manage affected Australian animal populations.
Slipping out unnoticed: a new bacterial lipoprotein transport system. Worldwide markets for biotechnology-derived products are projected to grow to at least $50 billion per year for the next 10 years. The cornerstone of biotechnology is the production of proteins. The applicant has discovered a new pathway for protein production in bacteria. The primary objective of this project is to use a diverse array of biochemical and biophysical techniques to understand how this new protein production pl ....Slipping out unnoticed: a new bacterial lipoprotein transport system. Worldwide markets for biotechnology-derived products are projected to grow to at least $50 billion per year for the next 10 years. The cornerstone of biotechnology is the production of proteins. The applicant has discovered a new pathway for protein production in bacteria. The primary objective of this project is to use a diverse array of biochemical and biophysical techniques to understand how this new protein production platform works. We will also assess this new pathway for the production of proteins of interest to the biotechnology sector. This project expects to determine how this system can be exploited for use in the growing Australian bioeconomy.Read moreRead less
Mapping cell wall and surface structures of Gram-positive cocci. The synthesis of the Gram-positive cell wall and protein transport are fundamental processes, the improved understanding of which will impact across a range of fields including microbiology, biochemistry and biotechnology, and the application and manipulation of Gram-positive bacteria in agriculture, industry and human health. In the long-term, the analysis of the Gram-positive ExPortal and cell wall will identify proteins that ma ....Mapping cell wall and surface structures of Gram-positive cocci. The synthesis of the Gram-positive cell wall and protein transport are fundamental processes, the improved understanding of which will impact across a range of fields including microbiology, biochemistry and biotechnology, and the application and manipulation of Gram-positive bacteria in agriculture, industry and human health. In the long-term, the analysis of the Gram-positive ExPortal and cell wall will identify proteins that may represent targets for therapeutic intervention. Additionally a precise understanding of the mechanisms of secretion of anchorless proteins will have an important impact in the biotechnology field, as new methodologies for the secretion of recombinant proteins of industrial value is a potential outcome.Read moreRead less
Safety in numbers: Bacterial aggregation and adaptation to oxidative stress. This project is a new collaboration which links two molecular microbiologists with the complementary skills required to make new insights into the molecular processes that underpin bacterial aggregation and biofilm formation. Biofilms are of immense significance in medical, industrial and environmental settings and so the fundamental information gained from this project will have wider relevance to the field of microbio ....Safety in numbers: Bacterial aggregation and adaptation to oxidative stress. This project is a new collaboration which links two molecular microbiologists with the complementary skills required to make new insights into the molecular processes that underpin bacterial aggregation and biofilm formation. Biofilms are of immense significance in medical, industrial and environmental settings and so the fundamental information gained from this project will have wider relevance to the field of microbiology. An outcome of this proposal will be fundamental knowledge about the production of surface adhesins that will form the basis for rational treatment of disease in the future. Prevention of aggregation and biofilm formation would make bacterial populations more susceptible to conventional antibiotic treatment.Read moreRead less
YhcB, a crucial player in the control of bacterial cell envelope biogenesis. All life depends on a cell envelope to enclose the chemical reactions that make life possible. But how do cell envelopes grow? How each component of the cell envelope is incorporated into the envelope at the right amount and in the right time to prevent cell death, has been a longstanding question in bacteriology. Using a unique combination of high through put genetic screens and biochemical approaches, this project wil ....YhcB, a crucial player in the control of bacterial cell envelope biogenesis. All life depends on a cell envelope to enclose the chemical reactions that make life possible. But how do cell envelopes grow? How each component of the cell envelope is incorporated into the envelope at the right amount and in the right time to prevent cell death, has been a longstanding question in bacteriology. Using a unique combination of high through put genetic screens and biochemical approaches, this project will characterise a key regulator of cell envelope growth in Gram-negative bacteria. Knowledge arising from this research will provide insight into a fundamental process in bacteria, will develop new technology to probe protein interactions, and will provide novel avenues to solve infection in plants, humans and animals.Read moreRead less
Molecular mechanisms of pilin glycosylation in Neisseria: a model system for protein glycosylation in bacteria. The disease causing bacteria Neisseria meningitidis and Neisseria gonorrhoeae are important human pathogens. Cell surface structures, called pili, are known to be important in allowing the bacteria to stick to host cells. Genetic and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. Until recently ....Molecular mechanisms of pilin glycosylation in Neisseria: a model system for protein glycosylation in bacteria. The disease causing bacteria Neisseria meningitidis and Neisseria gonorrhoeae are important human pathogens. Cell surface structures, called pili, are known to be important in allowing the bacteria to stick to host cells. Genetic and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. Until recently glycosylation of Gram-negative bacterial proteins was not thought to occur, however our recent work with these bacteria, and other groups studying Pseudomonas and Campylobacter, have shown that this process may be widespread. In our previous studies, we have identified and analysed a number of genes involved in pili glycosylation, in bacteria, which make known sugar structures. We have used this information to developed models for how the biochemistry and physiology of the glycosylation system may work. With a well-established structure and many genes already identified, glycosylation in Neisseria represents the best available model system to study this novel and important process. In the proposed study we describe experiments planned to test our models and reveal the molecular detail of this process. This study could lead to major advances in our understanding of this process and, when understood, may have future applications in biotechnology.Read moreRead less
Novel Babesia proteins and their roles in the pathogenesis of tick fever. This project aims at gaining a deep understanding of the biology of Babesia parasites and how they cause tick fever in cattle. The project expects to discover novel parasite proteins involved in the development and persistence of tick fever and identify their functional role in infection. The main expected outcome is the discovery of parasite proteins that are critical for infection and pathogenesis of cattle tick fever. T ....Novel Babesia proteins and their roles in the pathogenesis of tick fever. This project aims at gaining a deep understanding of the biology of Babesia parasites and how they cause tick fever in cattle. The project expects to discover novel parasite proteins involved in the development and persistence of tick fever and identify their functional role in infection. The main expected outcome is the discovery of parasite proteins that are critical for infection and pathogenesis of cattle tick fever. The findings will contribute to the development of future novel vaccines to control tick fever, with significant economic benefits for the beef and dairy industries worldwide.Read moreRead less
A next-generation whole parasite bovine Babesia vaccine. . In Australia, Babesia parasites cause most of the severe and often fatal cases of cattle-tick fever, a globally significant tick-borne disease. It can be prevented by a live-attenuated parasite vaccine which has critical limitations of a 4-day shelf-life and risk of severe disease if administered to adult cattle. This project aims to evaluate in cattle a novel whole parasite Babesia bovis vaccine that cannot cause disease and can be pres ....A next-generation whole parasite bovine Babesia vaccine. . In Australia, Babesia parasites cause most of the severe and often fatal cases of cattle-tick fever, a globally significant tick-borne disease. It can be prevented by a live-attenuated parasite vaccine which has critical limitations of a 4-day shelf-life and risk of severe disease if administered to adult cattle. This project aims to evaluate in cattle a novel whole parasite Babesia bovis vaccine that cannot cause disease and can be preserved as an off-the-shelf product without losing efficacy. The expected outcome is a significantly improved vaccine for a major infectious disease that affects primary food production. As the disease imposes a major economic burden, it will have great benefit for the Australian livestock industry.
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