Bacterial filamentation as a survival strategy: a goldmine for the discovery of new cell division regulators. The increasing emergence of untreatable bacterial infections is a serious threat to the health of Australians. Medical advances (organ transplants, chemotherapy), increases in diabetes, and an aging population increase the risk of infections caused by bacteria that are now resistant to most available antibiotics. New classes of antibiotics are urgently needed to treat these infections. T ....Bacterial filamentation as a survival strategy: a goldmine for the discovery of new cell division regulators. The increasing emergence of untreatable bacterial infections is a serious threat to the health of Australians. Medical advances (organ transplants, chemotherapy), increases in diabetes, and an aging population increase the risk of infections caused by bacteria that are now resistant to most available antibiotics. New classes of antibiotics are urgently needed to treat these infections. This project uses a novel approach to identify the mechanisms bacterial cells use to control their growth and avoid attack by our immune system. The research will identify potential targets for the development of new, effective antibiotics to kill multi-resistant bacteria, and ensure Australia's position at the forefront of infection control.Read moreRead less
A fundamental study of the role of signal transduction pathways in the regulation of Chlamydia's complex developmental cycle. Chlamydia are unique organisms in the microbial world. They are among the smallest bacteria and yet have a complex two-stage developmental cycle. In addition they are major causes of disease in animals and humans with no vaccines available. We have used the recent flood of full genome sequence data to identify over 30 new cell signalling proteins. By understanding how the ....A fundamental study of the role of signal transduction pathways in the regulation of Chlamydia's complex developmental cycle. Chlamydia are unique organisms in the microbial world. They are among the smallest bacteria and yet have a complex two-stage developmental cycle. In addition they are major causes of disease in animals and humans with no vaccines available. We have used the recent flood of full genome sequence data to identify over 30 new cell signalling proteins. By understanding how these cell signaling proteins are organized into pathways and how this microorganism controls its complex growth and developmental cycle, we will be able to develop novel methods of control. We are at the fore front of international research and therefore uniquely placed to conduct this project.Read moreRead less
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
Investigating the Ability of Honey to Inhibit Bacterial Biofilms Found in Chronic Wounds. Chronic (non-healing) wounds are a serious health problem in Australia. One quarter of our institutionalized aged population have pressure ulcers. The difficulty in treating these wounds is that most contain communities of bacteria, called biofilms, that are not killed by conventional antibiotics. Special honeys from Australia and NZ that are effective in chronic wound treatment can eradicate these biofilms ....Investigating the Ability of Honey to Inhibit Bacterial Biofilms Found in Chronic Wounds. Chronic (non-healing) wounds are a serious health problem in Australia. One quarter of our institutionalized aged population have pressure ulcers. The difficulty in treating these wounds is that most contain communities of bacteria, called biofilms, that are not killed by conventional antibiotics. Special honeys from Australia and NZ that are effective in chronic wound treatment can eradicate these biofilms. This project will identify the components in honey that do this and determine how they do it, to provide a more effective chronic wound treatment. It will decrease the prevalence of these wounds in Australia and the associated personal trauma and health costs.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
Kernel methods for the analysis of whole bacterial genomes. This project addresses the fundamental scientific problem of the identification of regulatory regions and specific promoters within bacterial genomes, with a focus upon two organisms of great social, economic and bioterrism significance. From the machine learning perspective, the project will be the first to produce a kernel-based approach directly tailored to the problem of the detection of regulatory regions. The methods developed wil ....Kernel methods for the analysis of whole bacterial genomes. This project addresses the fundamental scientific problem of the identification of regulatory regions and specific promoters within bacterial genomes, with a focus upon two organisms of great social, economic and bioterrism significance. From the machine learning perspective, the project will be the first to produce a kernel-based approach directly tailored to the problem of the detection of regulatory regions. The methods developed will be made available through a straightforward web-based interface, allowing biologists throughout the world to utilize the approach as a tool to be applied to a progressively widening class of bacterial genomes, and even to eukaryotes. 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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