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
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.
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
Development of a safe and immunogenic anti-chlamydia vaccine for the koala. Many koala populations are under threat of extinction from chlamydial disease.The project will develop a chlamydial vaccine and conduct trials in several wild koala populations for safety and effectiveness.
Discovery Early Career Researcher Award - Grant ID: DE230100700
Funder
Australian Research Council
Funding Amount
$429,449.00
Summary
A novel bacterial secretion system for applications in nanobiotechnology. This project aims to characterise a new molecular machine, called the S-Pump. Molecular machines drive the complex biology in all cells and are an exciting area of translational research, with broad potential for industrial applications. This project expects to provide fundamental insights into how bacterial S-Pumps contribute to antimicrobial resistance and enhancing food production. Expected outcomes include new tools fo ....A novel bacterial secretion system for applications in nanobiotechnology. This project aims to characterise a new molecular machine, called the S-Pump. Molecular machines drive the complex biology in all cells and are an exciting area of translational research, with broad potential for industrial applications. This project expects to provide fundamental insights into how bacterial S-Pumps contribute to antimicrobial resistance and enhancing food production. Expected outcomes include new tools for molecular machine discovery and identification of ways to adapt molecular machines for biotechnological applications. This work should enhance Australia-UK ties through collaboration, provide benefits toward nanobiotechnology and economic benefits through more efficient food production.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240100388
Funder
Australian Research Council
Funding Amount
$437,977.00
Summary
Ecological and phylogenomic insights into infectious diseases in animals. This project aims to address major knowledge gaps in our understanding of Clostridium difficile, a leading cause of severe gastrointestinal disease in animals. The project is expected to define the epidemiology of C. difficile infection in Australian horses, characterise the genetic and phenotypic traits of C. difficile strains causing equine disease and develop a new tool for enhanced genomic tracking of C. difficile in a ....Ecological and phylogenomic insights into infectious diseases in animals. This project aims to address major knowledge gaps in our understanding of Clostridium difficile, a leading cause of severe gastrointestinal disease in animals. The project is expected to define the epidemiology of C. difficile infection in Australian horses, characterise the genetic and phenotypic traits of C. difficile strains causing equine disease and develop a new tool for enhanced genomic tracking of C. difficile in animals. These outcomes will support strategies by the veterinary sector to improve the detection, prevention and control of C. difficile infections in animals, providing long-term socio-economic benefits arising from reduced incidence and mortality associated with C. difficile infections in Australian horses and livestock.Read 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.