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
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.
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
Structural Characterisation of the Type IX Secretion System. The Type IX Secretion System present in diverse bacteria of veterinary, agricultural, environmental and industrial importance enables effector proteins to be secreted and attached to the cell surface where they contribute to disease pathogenesis or degrade biopolymers of commercial interest. This project aims to determine the structure and assembly mechanism of this complex secretion nanomachine comprising 15 different proteins using s ....Structural Characterisation of the Type IX Secretion System. The Type IX Secretion System present in diverse bacteria of veterinary, agricultural, environmental and industrial importance enables effector proteins to be secreted and attached to the cell surface where they contribute to disease pathogenesis or degrade biopolymers of commercial interest. This project aims to determine the structure and assembly mechanism of this complex secretion nanomachine comprising 15 different proteins using state of the art microscopy. Knowledge of the structure will greatly enhance our understanding of secretion mechanisms and our ability to both inhibit the system to treat disease in animals or manipulate the system for industrial applications providing future economic and environmental benefits to our nation.Read moreRead less
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
Alphaherpesvirus recombination: safety implications for attenuated Herpesvirus vaccines. Under certain conditions some herpesviruses, including mild vaccine strains, can recombine to generate virulent viruses. Following findings that this occurred naturally between Australian poultry vaccines, with devastating results, this project will study natural herpesvirus recombination with the aim of allowing vaccines to be used more safely.
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
Evaluating host-parasite interplay in individual tissues. The immune system of the host and the infecting parasite has coevolved into a sophisticated balance of power. This project will explore this balance using Schistosoma japonicum infection in sheep and determine immune mechanisms unleashed by the host in various tissues as well as the response of the parasite to these attacks.
Antibacterial Material Design via Mechanism-Based Mathematical Modelling. This Project aims to provide new rules for the design of novel polymer materials with antibacterial properties by employing mechanism-based mathematical modelling.
This Project expects to generate new understanding of those mechanisms which underpin the antibacterial activity of these materials, how bacteria respond to these through metabolic changes and emergence of resistance.These rules will govern material design to yi ....Antibacterial Material Design via Mechanism-Based Mathematical Modelling. This Project aims to provide new rules for the design of novel polymer materials with antibacterial properties by employing mechanism-based mathematical modelling.
This Project expects to generate new understanding of those mechanisms which underpin the antibacterial activity of these materials, how bacteria respond to these through metabolic changes and emergence of resistance.These rules will govern material design to yield new antibacterial materials with improved properties.
Expected outcomes of this project may be a novel mechanism-based mathematical model that will enable the next-generation of antibacterial materials.
This outcome will help address the increasing economic and social burden of antibiotic drug resistance in Australia.
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