Phasevarions of Haemophilus influenzae: mechanisms and origins of a novel epigenetic system controlling coordinated random switching in expression of multiple genes. Central to the utilisation of biological information is our ability to identify and interpret DNA sequence information from genomes. In bacteria that cause disease, these investigations can identify key aspects of the infectious process or potential components of vaccines or new targets for antibiotics. Our recent work has identifie ....Phasevarions of Haemophilus influenzae: mechanisms and origins of a novel epigenetic system controlling coordinated random switching in expression of multiple genes. Central to the utilisation of biological information is our ability to identify and interpret DNA sequence information from genomes. In bacteria that cause disease, these investigations can identify key aspects of the infectious process or potential components of vaccines or new targets for antibiotics. Our recent work has identified a new genetic system, the 'phasevarion', that mediates random expression of multiple genes. The proposed research aims to advance our understanding of gene expression at the most basic level, revealing how bacteria generate diverse populations to evade environmental and immune stresses, and facilitating improved interpretation and use of DNA sequences for researchers and industry in this field.Read moreRead less
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
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
Genomic and molecular characterisation of a novel Australian leishmania pathogen. Leishmaniasis is the second most serious protozoal disease after malaria. This project will help characterise the first Leishmania species identified in Australia providing molecular tools to monitor the pathogen and a detailed assessment of any potential risk to human health. Comparative analysis with more pathogenic species will help identify genes and mechanisms that determine the progression of human disease le ....Genomic and molecular characterisation of a novel Australian leishmania pathogen. Leishmaniasis is the second most serious protozoal disease after malaria. This project will help characterise the first Leishmania species identified in Australia providing molecular tools to monitor the pathogen and a detailed assessment of any potential risk to human health. Comparative analysis with more pathogenic species will help identify genes and mechanisms that determine the progression of human disease leading to the potential identification of new drug and vaccine targets. The methodologies and expertise developed will be used will be available to other research groups working on infectious diseases.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
Next generation metagenomics. Applying the latest scientific advances supports society directly through promoting a knowledge based economy, as well as indirectly through securing agricultural productivity, improved biomedical applications and a greater understanding of our changing environment. Establishing these methods places Australia at the forefront of genomics technology with direct applications for Australian biomedical and biotechnology industries. Applying next generation sequencing fo ....Next generation metagenomics. Applying the latest scientific advances supports society directly through promoting a knowledge based economy, as well as indirectly through securing agricultural productivity, improved biomedical applications and a greater understanding of our changing environment. Establishing these methods places Australia at the forefront of genomics technology with direct applications for Australian biomedical and biotechnology industries. Applying next generation sequencing for metagenomics will provide a detailed understanding of microbial population structures and lead to advances in biomedicine, agriculture and environmental science. 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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Genetic and epigenetic control of developmental competence. Development is an important biological process of life and understanding development has important medical and economic benefits for Australia. This research aims to study development using a simple, easily manipulated and well established experimental organism, a fungus, as a model for development in other organisms, including humans. In addition, fungi directly impact on life at many levels. Fungi can be pathogens of humans, other ani ....Genetic and epigenetic control of developmental competence. Development is an important biological process of life and understanding development has important medical and economic benefits for Australia. This research aims to study development using a simple, easily manipulated and well established experimental organism, a fungus, as a model for development in other organisms, including humans. In addition, fungi directly impact on life at many levels. Fungi can be pathogens of humans, other animals or plants significantly affecting our health, agriculture and industry. Fungi are also beneficial to other organisms, especially to many plants, and are used to manufacture pharmaceuticals and enzymes used in the health and biotechnology industries.Read moreRead less