Identifying Novel Biosynthetic Pathways in Mycobacteria using DNA Microarray Technology. DNA microarrays are a powerful new bioinformatics-based technology and an ideal tool for characterising complex biosynthetic pathways since the expression of all genes in the bacterial genome can be monitored in a single experiment. In this project we aim to construct and use a DNA microarray to identify novel biosynthetic pathways in mycobacteria. Of particular interest are pathways used to create compone ....Identifying Novel Biosynthetic Pathways in Mycobacteria using DNA Microarray Technology. DNA microarrays are a powerful new bioinformatics-based technology and an ideal tool for characterising complex biosynthetic pathways since the expression of all genes in the bacterial genome can be monitored in a single experiment. In this project we aim to construct and use a DNA microarray to identify novel biosynthetic pathways in mycobacteria. Of particular interest are pathways used to create components of the highly complex and poorly characterised cell wall. Since this structure is unique in the bacterial world, we expect to identify and characterise pathways that are unique to mycobacteria.Read moreRead less
Autotransporter proteins of Escherichia coli. Autoransporters are a novel class of proteins associated with bacterial virulence properties such as adhesion, invasion and biofilm formation. Despite this, limited information is available on their functional role. The aim of this project is to characterize several of the autotransporter proteins from pathogenic E. coli. The likely contribution of these proteins to infection suggests that they are potential targets for strain attenuation and vaccine ....Autotransporter proteins of Escherichia coli. Autoransporters are a novel class of proteins associated with bacterial virulence properties such as adhesion, invasion and biofilm formation. Despite this, limited information is available on their functional role. The aim of this project is to characterize several of the autotransporter proteins from pathogenic E. coli. The likely contribution of these proteins to infection suggests that they are potential targets for strain attenuation and vaccine strain construction. Many of these proteins also mediate bacterial aggregation and are therefore targets for novel drugs that inhibit this process. The project will be carried out with a high profile partner from Denmark and will provide opportunity for travel and technology development. 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
Host cell targets of bacterial virulence effectors. The research described in this proposal will result in a better understanding of the cell biology of host-pathogen interactions. We are in a unique position to analyze the importance of protein/protein interactions between bacterial virulence determinants and host cell proteins using a range of cell biology techniques to address the fundamental, molecular basis of the host-pathogen interaction. In addition we will construct a new genetic tool ....Host cell targets of bacterial virulence effectors. The research described in this proposal will result in a better understanding of the cell biology of host-pathogen interactions. We are in a unique position to analyze the importance of protein/protein interactions between bacterial virulence determinants and host cell proteins using a range of cell biology techniques to address the fundamental, molecular basis of the host-pathogen interaction. In addition we will construct a new genetic tool to identify novel bacterial virulence determinants. We anticipate that a greater knowledge of the factors that contribute to the host-pathogen interaction will provide new insights into the subversion of host cell processes by bacterial pathogens of animals, plants and humans.
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Disulfide catalysis and protein folding in bacterial virulence. The molecular mechanisms that underpin disulfide bond formation have had a major impact on our understanding of protein folding and function. This project will make a major contribution to fundamental areas of disulfide catalysis pathways in bacterial pathogens and thus help maintain a strong international profile for Australian research in this field. The work will lead to training of research scientists and students in techniques ....Disulfide catalysis and protein folding in bacterial virulence. The molecular mechanisms that underpin disulfide bond formation have had a major impact on our understanding of protein folding and function. This project will make a major contribution to fundamental areas of disulfide catalysis pathways in bacterial pathogens and thus help maintain a strong international profile for Australian research in this field. The work will lead to training of research scientists and students in techniques that include molecular genetics, protein biochemistry and structural biology. Our findings may impact future directions for vaccine research on pathogens that cause life threatening infections in humans and therefore lead to improved health and reduced health care expenditure.Read moreRead less
Evolutionary and ecological complexity in an experimentally controlled environment. Understanding the capacity and mechanism of microbial evolution provides the framework for developing new strategies for preventing infectious disease. If we know how evolution works, it will be possible to hamper the capacity to evolve as a mechanism of preventing new diseases and controlling existing ones. This project will provide a mechanistic description of evolution in real time under controlled conditions. ....Evolutionary and ecological complexity in an experimentally controlled environment. Understanding the capacity and mechanism of microbial evolution provides the framework for developing new strategies for preventing infectious disease. If we know how evolution works, it will be possible to hamper the capacity to evolve as a mechanism of preventing new diseases and controlling existing ones. This project will provide a mechanistic description of evolution in real time under controlled conditions. This detailed information will be used in the education of the public and in debates about evolution. The project will also train at least five students in molecular and evolutionary microbiology, essential for facing future challenges.
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Synthesis and assembly of bacterial repeat unit polysaccharides. Bacteria make an enormous range of surface polysaccharides. The complexity was first appreciated as antigenic diversity, but we now have hundreds of chemical structures and perhaps a hundred sequences of their gene clusters, but the number in nature must be many thousands. Our knowledge of gene function is growing but is not keeping up with the discovery of new sequences and structures. The aim is to determine structure and functio ....Synthesis and assembly of bacterial repeat unit polysaccharides. Bacteria make an enormous range of surface polysaccharides. The complexity was first appreciated as antigenic diversity, but we now have hundreds of chemical structures and perhaps a hundred sequences of their gene clusters, but the number in nature must be many thousands. Our knowledge of gene function is growing but is not keeping up with the discovery of new sequences and structures. The aim is to determine structure and function of key O antigen processing genes and the functions of a range of glycosyl transferases, and to use the information to generate novel gene clusters to synthesise novel polysaccharidesRead moreRead less
Elucidation of bacterial glycosylytransferase specificity. The benefits are involvement in the growth area of polysaccharide research, with potential for major industrial spin off. Polysaccharides are critical in all organisms as signalling, structural and storage compounds. Bacteria make a wide variety with extensive use of unusual sugars, some with uses from oil emulsifiers to food thickeners. The project is on the enzymes that assemble bacterial polysaccharides. We are world leaders in genet ....Elucidation of bacterial glycosylytransferase specificity. The benefits are involvement in the growth area of polysaccharide research, with potential for major industrial spin off. Polysaccharides are critical in all organisms as signalling, structural and storage compounds. Bacteria make a wide variety with extensive use of unusual sugars, some with uses from oil emulsifiers to food thickeners. The project is on the enzymes that assemble bacterial polysaccharides. We are world leaders in genetics of the gene clusters especially synthesis of the unusual sugars. We now aim to fill a major gap by determining which enzymes make which bonds, leading to options for new gene combinations and novel structures. We have a lead in research in this area and Australia gains if we maintain that lead.Read moreRead less
The Fine Tuned Physiology of Microaerophilic Gastric Spirilla. The aim of the project is to understand the molecular basis of fundamental properties of the physiology of enterogastric spiral bacteria of the genera Campylobacter and Helicobacter. The characteristics of these obligate microaerophiles which will be investigated are their aerobic respiratory chains, the special metabolites and enzymes involved in thiol-disulphide redox balance, and their essential requirement for carbon dioxide. Mic ....The Fine Tuned Physiology of Microaerophilic Gastric Spirilla. The aim of the project is to understand the molecular basis of fundamental properties of the physiology of enterogastric spiral bacteria of the genera Campylobacter and Helicobacter. The characteristics of these obligate microaerophiles which will be investigated are their aerobic respiratory chains, the special metabolites and enzymes involved in thiol-disulphide redox balance, and their essential requirement for carbon dioxide. Microaerobes include some bacteria, archea and protozoa. Realisation of the widespread habitats and importance of microaerophiles, has led recently to a vigorous interest in understanding their physiology. Knowledge of the basic properties of microaerophily has potential applications to Environmental Microbiology, Agriculture, Industrial Microbiology, Veterinary Science and Medicine.Read moreRead less
Structure and function of novel transporters in alphaproteobacteria. First, detailed knowledge of a set of membrane transporters and the way their activity might be inhibited, will have implications for the treatment of human disease. Second, excellent outcomes are provided for the training of postgraduate students and research staff. This project entails cutting edge technology, and the transfer of technical capabilities not currently available in Australia. Third, our studies on non-pathogenic ....Structure and function of novel transporters in alphaproteobacteria. First, detailed knowledge of a set of membrane transporters and the way their activity might be inhibited, will have implications for the treatment of human disease. Second, excellent outcomes are provided for the training of postgraduate students and research staff. This project entails cutting edge technology, and the transfer of technical capabilities not currently available in Australia. Third, our studies on non-pathogenic species of alpha-proteobacteria provides for a timely advance in our knowledge of their biology: other species of alpha-proteobacteria were amongst the first organisms trialled for biological weapons by the USA and the former Soviet Union, and those pathogenic species are rated as Class 3 organisms.Read moreRead less