Variation in bacterial genomic mutation rates. Our measurement of global mutation rates will contribute to an understanding of the evolutionary properties of bacteria, the most diverse and successful organisms in the biosphere. Bacterial variation and culture richness contributes not only to ecological processes but also to emerging diseases. The studies will enhance capabilities essential in interpreting the evolution of epidemics and the kinetics of bacterial sweeps in nature. Variation also p ....Variation in bacterial genomic mutation rates. Our measurement of global mutation rates will contribute to an understanding of the evolutionary properties of bacteria, the most diverse and successful organisms in the biosphere. Bacterial variation and culture richness contributes not only to ecological processes but also to emerging diseases. The studies will enhance capabilities essential in interpreting the evolution of epidemics and the kinetics of bacterial sweeps in nature. Variation also provides the source material for exploitation of bacterial products such as antibiotics. The results from understanding a complete set of mutational changes through genomic analysis will provide the most direct estimates of variation in evolving bacteria.Read moreRead less
Detection of imported exotic strains of West Nile virus for national biosecurity surveillance. West Nile virus (WNV) is transmitted by mosquitoes and causes a fatal disease of the brain in animals and humans. WNV is currently exotic to this country, however a closely related, but benign cousin of this virus (Kunjin) can be found in Northern Australia. Currently it is very difficult to differentiate between infections with WNV and Kunjin using standard laboratory tests, therefore it will be diff ....Detection of imported exotic strains of West Nile virus for national biosecurity surveillance. West Nile virus (WNV) is transmitted by mosquitoes and causes a fatal disease of the brain in animals and humans. WNV is currently exotic to this country, however a closely related, but benign cousin of this virus (Kunjin) can be found in Northern Australia. Currently it is very difficult to differentiate between infections with WNV and Kunjin using standard laboratory tests, therefore it will be difficult for public health officials to detect WNV if it is introduced to Australia. In this project we aim to develop more accurate laboratory tests to detect infections with the deadly, exotic WNV using new strategies. 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
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
A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a ....A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a role in the development of diabetes in humans. In plants, sugars affect many processes including growth, flowering, photosynthesis, nitrogen metabolism, starch synthesis, pigmentation and response to pathogens.Read moreRead less
New drugs for malaria that target histone deacetylases. There is no vaccine for malaria and current drugs are failing, contributing to millions of malaria-related deaths each year. The aim of this project is to develop new drugs to address this significant global health issue. This project will focus on drugs that act in novel ways to existing malaria drugs by targeting enzymes that are involved in altering gene expression in the parasite. These kinds of enzymes are recognised drug targets in ot ....New drugs for malaria that target histone deacetylases. There is no vaccine for malaria and current drugs are failing, contributing to millions of malaria-related deaths each year. The aim of this project is to develop new drugs to address this significant global health issue. This project will focus on drugs that act in novel ways to existing malaria drugs by targeting enzymes that are involved in altering gene expression in the parasite. These kinds of enzymes are recognised drug targets in other diseases such as cancer. The outcomes of this project will include advances in malaria drug development that build on Australian drug discovery efforts, seeding further funding opportunities from industry and other sources and contributing research training and capacity building in Australia.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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Environmental influence on evolutionary processes in bacterial populations. Bacterial populations exhibit remarkable adaptive capabilities in many environmental and medical settings. They respond to environmental stress in terms of altered gene expression, but what are the effects on mutation rates and fitness when cells grow at suboptimal growth rates? We plan to test whether the physiological state of an ancestral population is a determinant of a population's subsequent response to selection. ....Environmental influence on evolutionary processes in bacterial populations. Bacterial populations exhibit remarkable adaptive capabilities in many environmental and medical settings. They respond to environmental stress in terms of altered gene expression, but what are the effects on mutation rates and fitness when cells grow at suboptimal growth rates? We plan to test whether the physiological state of an ancestral population is a determinant of a population's subsequent response to selection. A simple model system using controlled culture conditions will be used to investigate the linkage between environment, mutation rate and fitness under selection. Demonstration of these linkages will have significant impacts on microbiology and understanding evolution.Read moreRead less
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