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.
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
Autotransporter folding: insights advancing recombinant protein production. Imagine a world in which any protein could be produced using a single production platform. This project aims to make this a reality by reengineering autotransporters, a large family of bacterial virulence factors with a modular structure that makes them amenable to rational design. The project plans to examine the structures and folding behaviour of autotransporters and reengineered derivatives fused to target heterologo ....Autotransporter folding: insights advancing recombinant protein production. Imagine a world in which any protein could be produced using a single production platform. This project aims to make this a reality by reengineering autotransporters, a large family of bacterial virulence factors with a modular structure that makes them amenable to rational design. The project plans to examine the structures and folding behaviour of autotransporters and reengineered derivatives fused to target heterologous proteins using biochemical, biophysical, and structural methods. It is expected that this project will provide fundamental insights into factors that dictate autotransporter folding and stability, which may enhance recombinant protein production and drive discovery of strategies to prevent autotransporter-mediated infection.Read moreRead less
Unravelling small RNA regulatory networks to target and control bacteria. Small RNA (sRNA) molecules are critical regulators of bacterial gene expression. These molecules control important phenotypes in the Gram-negative veterinary pathogen Pasteurella multocida. This project aims to identify the range of P. multocida sRNAs and to show how expression of these molecules changes under various growth conditions. Specifically, this project endeavours: to identify the mRNA targets of the sRNAs; to id ....Unravelling small RNA regulatory networks to target and control bacteria. Small RNA (sRNA) molecules are critical regulators of bacterial gene expression. These molecules control important phenotypes in the Gram-negative veterinary pathogen Pasteurella multocida. This project aims to identify the range of P. multocida sRNAs and to show how expression of these molecules changes under various growth conditions. Specifically, this project endeavours: to identify the mRNA targets of the sRNAs; to identify the mechanisms of sRNA-mRNA interaction; to build systems-biology models that describe the sRNA regulatory circuits; to design inhibitors capable of disrupting critical sRNA-mRNA interactions; and to use the new inhibitors to modulate specific phenotypes. The ability to precisely manipulate sRNA regulatory circuits could allow fine control of bacterial phenotypes and could be widely applicable.Read moreRead less
A link between antibiotic resistance and bacterial sporulation. This project aims to define the sporulation process in the bacterium Clostridium difficile, and advance our understanding of a link between antibiotic use and sporulation. To survive in hostile environments, some bacteria produce a dormant and resilient cell form called a spore which can survive for many years in unfavourable environments, but our understanding of how this process occurs is limited. This project will provide a deepe ....A link between antibiotic resistance and bacterial sporulation. This project aims to define the sporulation process in the bacterium Clostridium difficile, and advance our understanding of a link between antibiotic use and sporulation. To survive in hostile environments, some bacteria produce a dormant and resilient cell form called a spore which can survive for many years in unfavourable environments, but our understanding of how this process occurs is limited. This project will provide a deeper understanding of the sporulation process and the long-lasting detrimental impact of antibiotic use. The project expects to provide economic benefits, reduce environmental microbial contamination and contribute to better health of animals and humans.Read moreRead less
Recombinant probiotics for prevention of enteric infections in piglets. Shigatoxigenic and enterotoxigenic strains of Escherichia coli cause severe diarrhoeal disease and oedema disease in piglets. The resultant morbidity and mortality is a major cause of financial loss to the pig industry both in Australia and overseas. We have conceived a highly novel approach to prevention of these diseases involving molecular mimicry of host receptors for the E. coli toxins and adhesins on the surface of a ....Recombinant probiotics for prevention of enteric infections in piglets. Shigatoxigenic and enterotoxigenic strains of Escherichia coli cause severe diarrhoeal disease and oedema disease in piglets. The resultant morbidity and mortality is a major cause of financial loss to the pig industry both in Australia and overseas. We have conceived a highly novel approach to prevention of these diseases involving molecular mimicry of host receptors for the E. coli toxins and adhesins on the surface of a harmless bacterium. Oral administration of this agent to piglets has the potential to bind free toxins in the gut and prevent colonization of the intestines by the pathogens, thereby preventing disease.Read moreRead less
Vaccine against leptospirosis. This project will utilise the information from the determination of the complete genome sequence of Leptospira borgpetersenii serovar Hardjobovis at Monash University. Bioinformatics analysis will be used to allow a global approach to identify all putative vaccine antigens which will be cloned, expressed and purified and their protective capacity investigated.
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.
Mitochondria: a target for intracellular bacterial pathogens. This project aims to understand how intracellular bacterial pathogens target mitochondria. Coxiella burnetii is a unique and significant pathogen of humans and commercially important animals that uses effector proteins to control host cell functions. A cohort of these effectors target mitochondria. Since mitochondria are key players in cell health, the intended outcome of this research is to understand the role of the mitochondrially- ....Mitochondria: a target for intracellular bacterial pathogens. This project aims to understand how intracellular bacterial pathogens target mitochondria. Coxiella burnetii is a unique and significant pathogen of humans and commercially important animals that uses effector proteins to control host cell functions. A cohort of these effectors target mitochondria. Since mitochondria are key players in cell health, the intended outcome of this research is to understand the role of the mitochondrially-targeted effector proteins. The project will determine the importance of mitochondrial protein trafficking for Coxiella pathogenesis and how mitochondrial function is altered during infection. This will provide understanding of how bacterial pathogens manipulate organelles like mitochondria for their survival.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