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
Molecular pumps and metabolism: regulatory interactions that control metal uptake and metabolism in bacteria. ABC (ATP-Binding Cassette) transporters are ubiquitous pumps that transport small molecules into and out of cells. This project investigates the novel roles of small-molecule-binding domains in the protein machine that drives the transporters for molybdenum and iron. They are predicted to interact with regulatory proteins and integrate transport with metabolism. It will provide insights ....Molecular pumps and metabolism: regulatory interactions that control metal uptake and metabolism in bacteria. ABC (ATP-Binding Cassette) transporters are ubiquitous pumps that transport small molecules into and out of cells. This project investigates the novel roles of small-molecule-binding domains in the protein machine that drives the transporters for molybdenum and iron. They are predicted to interact with regulatory proteins and integrate transport with metabolism. It will provide insights into metal trafficking and characterize gene regulatory networks that are important for bacterial pathogenicity and biological nitrogen fixation.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
Exploiting microbial metabolites to understand fungal biology. The project aims to investigate the principles of hyphal growth in fungi, by studying the mechanisms of action of a bacteria-derived compound that inhibits hyphae. Changing cell shape between yeast and hyphae is a prototype developmental switch enabling fungi to escape stressful environments, while hyphal invasion promotes fungal infections of animals and plants that endanger food security and biodiversity. By using interdisciplinary ....Exploiting microbial metabolites to understand fungal biology. The project aims to investigate the principles of hyphal growth in fungi, by studying the mechanisms of action of a bacteria-derived compound that inhibits hyphae. Changing cell shape between yeast and hyphae is a prototype developmental switch enabling fungi to escape stressful environments, while hyphal invasion promotes fungal infections of animals and plants that endanger food security and biodiversity. By using interdisciplinary approaches of microbiology and chemistry, the expected outcomes are to generate deep knowledge of an important microbial process and how it could be modulated, characterise a new bacterial compound and build research capacity at the nexus of biology and chemistry to benefit discoveries in academia and industry.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
Arsenite oxidation by a novel bacterium that is a candidate for arsenic bioremediation. The arsenic munching microbe NT-26 could help in the fight to clean up arsenic-contaminated mining waste and drinking water. Arsenic poses an environmental problem in countries such as Australia, USA and Canada owing primarily to mining activities. The problem in countries such as Bangladesh and West Bengal are even more serious as these people are dying of arsenic-related diseases as they rely on water conta ....Arsenite oxidation by a novel bacterium that is a candidate for arsenic bioremediation. The arsenic munching microbe NT-26 could help in the fight to clean up arsenic-contaminated mining waste and drinking water. Arsenic poses an environmental problem in countries such as Australia, USA and Canada owing primarily to mining activities. The problem in countries such as Bangladesh and West Bengal are even more serious as these people are dying of arsenic-related diseases as they rely on water containing arsenic as their primary source of drinking water. The outcomes of this research should provide the necessary information for removing arsenic from all types of waters.Read moreRead less
Defining the antiviral effects of Wolbachia in Aedes aegypti mosquitoes. Mosquitoes that carry a bacterium called Wolbachia do not transmit human pathogenic viruses. These mosquitoes are being developed as a biocontrol tool to prevent mosquito-borne diseases. This project aims to define the molecular basis for virus inhibition by Wolbachia. Using unique biological tools including mosquitoes carrying different strains of Wolbachia that do or do not inhibit dengue virus, the project will define ho ....Defining the antiviral effects of Wolbachia in Aedes aegypti mosquitoes. Mosquitoes that carry a bacterium called Wolbachia do not transmit human pathogenic viruses. These mosquitoes are being developed as a biocontrol tool to prevent mosquito-borne diseases. This project aims to define the molecular basis for virus inhibition by Wolbachia. Using unique biological tools including mosquitoes carrying different strains of Wolbachia that do or do not inhibit dengue virus, the project will define how Wolbachia modifies its host to create an antiviral state. The findings will provide insight into how viral pathogens can be suppressed in insect hosts. This may guide future viral disease intervention strategies for diverse areas afflicted by insect-borne viral disease, including human health and agriculture.Read moreRead less
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