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.
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.
Molecular characterisation of antibiotic resistance genes in Salmonella enterica and Escherichia coli recovered from food-producing animals and humans. Antibiotic resistance is an accelerating global problem. Antibiotic resistance genes are located on mobile genetic elements which can be horizontally transferred between distantly related bacteria. It is becoming increasingly apparent that healthy humans carry populations of resistant bacteria as part of the normal microbial flora. This project w ....Molecular characterisation of antibiotic resistance genes in Salmonella enterica and Escherichia coli recovered from food-producing animals and humans. Antibiotic resistance is an accelerating global problem. Antibiotic resistance genes are located on mobile genetic elements which can be horizontally transferred between distantly related bacteria. It is becoming increasingly apparent that healthy humans carry populations of resistant bacteria as part of the normal microbial flora. This project will characterise the antibiotic resistance gene arrangements among populations of bacteria which belong to the Enterobacteriaceae. These resistant bacteria represent a threat to human and veterinary health because they are readily ingested as part of the food chain and represent reservoirs for the spread of antibiotic resistance genes to pathogens.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 domains within Mycoplasma hyopneumoniae surface proteins that interact with host extracellular matrix: efficacy testing of candidate vaccines in swine. Over 90% of Australian commercial pig production facilities are affected by Mycoplasma hyopneumoniae, the causative agent of swine enzootic pneumonia. This disease causes economic losses in Australia of over $20 million per annum and up to $1 billion per annum in major swine rearing countries worldwide. This project will determine the p ....Defining domains within Mycoplasma hyopneumoniae surface proteins that interact with host extracellular matrix: efficacy testing of candidate vaccines in swine. Over 90% of Australian commercial pig production facilities are affected by Mycoplasma hyopneumoniae, the causative agent of swine enzootic pneumonia. This disease causes economic losses in Australia of over $20 million per annum and up to $1 billion per annum in major swine rearing countries worldwide. This project will determine the protective efficacy of new generation vaccines against M. hyopneumoniae, which aim to block the colonisation process and prevent disease .Read moreRead less
Autotransporter proteins of enterohemorrhagic Escherichia coli O157:H7. Escherichi (E.) coli O157:H7 has caused hundreds of outbreaks in the United States and United Kingdom. Although not currently a major problem in Australia, the emergence of E. coli O157:H7 here would have serious implications for our meat and livestock industry. This study will provide important information for the selection of vaccine antigens used to prevent the colonisation of cattle with E. coli O157:H7 and other diarrho ....Autotransporter proteins of enterohemorrhagic Escherichia coli O157:H7. Escherichi (E.) coli O157:H7 has caused hundreds of outbreaks in the United States and United Kingdom. Although not currently a major problem in Australia, the emergence of E. coli O157:H7 here would have serious implications for our meat and livestock industry. This study will provide important information for the selection of vaccine antigens used to prevent the colonisation of cattle with E. coli O157:H7 and other diarrhoeagenic E. coli serotypes. A direct outcome of this will be improved human health, as E. coli O157:H7 can cause life threatening infections in humans. The study will also examine the contribution of specific adhesins to biofilm formation; measures to prevent biofilm formation may reduce the persistence and spread of E. coli O157:H7 in the environment.Read moreRead less
Identification and characterisation of Mycoplasma hyopneumoniae surface-molecules that interact with the host epithelium. Mycoplasma hyponeumoniae causes porcine enzootic pneumonia, a disease that significantly impacts swine production. Current vaccines are unable to prevent colonisation of the respiratory tract and are costly to produce and administer. The expression of microbial adhesins that mediate adherence to the extracellular matrix is considered the initial step in host colonisation for ....Identification and characterisation of Mycoplasma hyopneumoniae surface-molecules that interact with the host epithelium. Mycoplasma hyponeumoniae causes porcine enzootic pneumonia, a disease that significantly impacts swine production. Current vaccines are unable to prevent colonisation of the respiratory tract and are costly to produce and administer. The expression of microbial adhesins that mediate adherence to the extracellular matrix is considered the initial step in host colonisation for many bacterial pathogens. We propose to identify M. hyopneumoniae cell surface moleculaes that interact with components of the extracellular matrix. Targetting these cell surface molecules will lead to therapeutics that prevent disease and block colonisation, eventually eradicating the host pathogen from pig production facilities.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