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 comprehensive analysis of the outer membrane, surface exposed and secreted proteome of Pasteurella multocida. Pasteurella multocida is the causative agent of a range of animal diseases. The molecular mechanisms of P. multocida pathogenesis are poorly understood and the current vaccines generally ineffective. We will identify all P. multocida outer membrane, surface exposed and secreted proteins expressed during natural infection, or under conditions which mimic natural infection, by a global p ....A comprehensive analysis of the outer membrane, surface exposed and secreted proteome of Pasteurella multocida. Pasteurella multocida is the causative agent of a range of animal diseases. The molecular mechanisms of P. multocida pathogenesis are poorly understood and the current vaccines generally ineffective. We will identify all P. multocida outer membrane, surface exposed and secreted proteins expressed during natural infection, or under conditions which mimic natural infection, by a global proteomics approach. We believe that secreted proteins and those found on the outer surface of the bacterial cell are likely to be crucial virulence determinants. The expected outcomes are the identification of a number of candidate vaccine antigens and an enhanced understanding of Pasteurella pathogenesis.Read moreRead less
Discovery of Novel Bacteriophage with the Capacity to Modulate Gut Bacteria. This project aims to experimentally validate the largest ever collection of bacterial viruses (bacteriophages) within the gut microbiome. This project expects to generate new knowledge in the area of bacteriophage biology and genomics by using the innovative approaches of wet-lab and bioinformatic genome analyses. Expect outcomes of this project include the discovery of novel phages using bioinformatics, wet-lab validat ....Discovery of Novel Bacteriophage with the Capacity to Modulate Gut Bacteria. This project aims to experimentally validate the largest ever collection of bacterial viruses (bacteriophages) within the gut microbiome. This project expects to generate new knowledge in the area of bacteriophage biology and genomics by using the innovative approaches of wet-lab and bioinformatic genome analyses. Expect outcomes of this project include the discovery of novel phages using bioinformatics, wet-lab validation of their activity and characterisation of their potential to contribute new bacterial host metabolism. This should provide benefits, such as advancement to our understanding of bacteriophages, improved bioinformatic software, and a characterised collection of commercially valuable bacterial strains and phages.Read moreRead less
The role of virulence factors of Clostridium difficile in food animals. Disease caused by the bacterium Clostridium difficile are a significant food production animal and public health problem in many countries. Specific animal and human public health resources have been allocated in many countries in efforts to mitigate the growing epidemics. The study proposed in this application presents a significant opportunity to learn about the virulence factors of animal strains of this bacterium about w ....The role of virulence factors of Clostridium difficile in food animals. Disease caused by the bacterium Clostridium difficile are a significant food production animal and public health problem in many countries. Specific animal and human public health resources have been allocated in many countries in efforts to mitigate the growing epidemics. The study proposed in this application presents a significant opportunity to learn about the virulence factors of animal strains of this bacterium about which very little is known. This project will lead to rationally designed preventative and treatment strategies that apply to both animals and humans, thereby impeding epidemics caused by C. difficile in Australia.Read moreRead less
Pathogenesis, regulation and genomics of the ovine footrot pathogen, Dichelobacter nodosus. Footrot is one of the most economically significant diseases of sheep in Australia. The aim of this project is to develop a detailed understanding of how the bacterium that causes this infection is able to infect the sheep hoof and result in clinical disease. The complete sequence of the genome of the causative bacterium will be determined, enabling us to deduce its genetic potential. The completed projec ....Pathogenesis, regulation and genomics of the ovine footrot pathogen, Dichelobacter nodosus. Footrot is one of the most economically significant diseases of sheep in Australia. The aim of this project is to develop a detailed understanding of how the bacterium that causes this infection is able to infect the sheep hoof and result in clinical disease. The complete sequence of the genome of the causative bacterium will be determined, enabling us to deduce its genetic potential. The completed project will significantly advance fundamental knowledge of the disease process and will lead to the development of improved methods for the control of the disease, with concomitant cost savings to Australian primary industry.Read moreRead less
Proteomics and vaccine development in swine dysentery. Swine dysentery is an infectious disease of significant economic importance caused by Brachyspira hyodysenteriae. There is no effective vaccine available. This project will combine modern techniques in microbial genomics and proteomics to identify outer membrane proteins of B. hyodysenteriae and evaluate their role as candidate vaccine antigens.
How bacteria form resistant aggregates and biofilms. This research aims to use interdisciplinary approaches to advance fundamental knowledge on bacterial aggregates and biofilms. These bacterial clusters are a significant problem as they have extraordinary resistance to disinfectants and antibiotics, and currently no effective methods are available to disrupt them. The expected outcomes of this project are to dissect how autotransporters, the most common group of bacterial cell-surface proteins, ....How bacteria form resistant aggregates and biofilms. This research aims to use interdisciplinary approaches to advance fundamental knowledge on bacterial aggregates and biofilms. These bacterial clusters are a significant problem as they have extraordinary resistance to disinfectants and antibiotics, and currently no effective methods are available to disrupt them. The expected outcomes of this project are to dissect how autotransporters, the most common group of bacterial cell-surface proteins, promote aggregation and biofilm formation, and to develop inhibitors that prevent the formation of these damaging bacterial clusters. Ultimately, this new knowledge will help address the increasing economic and social burden of industrial, environmental and biomedical biofilms.Read moreRead less
Vaccination of poultry infected with multiple Salmonella serovars. Salmonella is a zoonotic, foodborne pathogen found on eggs and poultry meat. It is the second largest cause of human gastrointestinal disease, thus, reduction of Salmonella on poultry farms is paramount to public health. This project aims to evaluate the long-term efficacy of a commercial Salmonella Typhimurium vaccine against multiple serotypes, including the emerging Salmonella Enteritidis. This project will generate new knowle ....Vaccination of poultry infected with multiple Salmonella serovars. Salmonella is a zoonotic, foodborne pathogen found on eggs and poultry meat. It is the second largest cause of human gastrointestinal disease, thus, reduction of Salmonella on poultry farms is paramount to public health. This project aims to evaluate the long-term efficacy of a commercial Salmonella Typhimurium vaccine against multiple serotypes, including the emerging Salmonella Enteritidis. This project will generate new knowledge in avian immunology using an innovative approach to evaluate the host response to multi-serovar infection. Outcomes of this project will future proof the Australian poultry industry against exotic Salmonella serotypes benefitting the industry by significantly reducing risks of future outbreaks and economic loss.Read moreRead less
Unraveling autotransporter function in bacterial aggregates and biofilms. Autotransporters are a large family of bacterial proteins that play a central role in pathogenesis. They promote the formation of cell clusters and biofilms, which are mechanisms for bacterial resistance to host immune factors and antibiotics. Currently, the precise mode of action of autotransporters is unknown. This project will examine the interplay between the structure and function of key autotransporter proteins. It ....Unraveling autotransporter function in bacterial aggregates and biofilms. Autotransporters are a large family of bacterial proteins that play a central role in pathogenesis. They promote the formation of cell clusters and biofilms, which are mechanisms for bacterial resistance to host immune factors and antibiotics. Currently, the precise mode of action of autotransporters is unknown. This project will examine the interplay between the structure and function of key autotransporter proteins. It is expected that the outcomes of this research will establish how these proteins mediate aggregation and biofilm formation. It may also provide three-dimensional structures of proteins that are strongly immunogenic and may represent targets for future vaccine design, as well as identify molecules that inhibit autotransporter function.Read moreRead less
Transport and innate immune properties of DNA in bacterial nano-sized vesicles. All types of living organisms release nano-sized membrane vesicles or “blebs” which they use for intercellular communication and transport of molecules. This project will determine how bacteria package DNA within these vesicles, how this DNA is transported into host cells and how it triggers immune responses in these cells.