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
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
Effect of predation on virulence traits of opportunistic pathogens. The project aims to determine if increased fitness of bacteria in animal or human hosts (increased virulence) can occur due to indirect rather than direct selective pressure, particularly pressure on bacteria arising from predation by protozoa. Protozoa feed on many pathogenic bacteria (e.g. those that cause cholera and chronic infections) in the ocean, and warming oceans are predicted to increase predation. Knowing the effect o ....Effect of predation on virulence traits of opportunistic pathogens. The project aims to determine if increased fitness of bacteria in animal or human hosts (increased virulence) can occur due to indirect rather than direct selective pressure, particularly pressure on bacteria arising from predation by protozoa. Protozoa feed on many pathogenic bacteria (e.g. those that cause cholera and chronic infections) in the ocean, and warming oceans are predicted to increase predation. Knowing the effect of warming oceans on marine bacteria and the emergence of virulence in bacteria that are subject to predation in the environment can inform design of tools for monitoring the risk of infection outbreaks. Benefits would be realised by academic researchers, clinicians and policy-makers interested in optimising the tracking of infection threats.Read moreRead less
Importance of Wzx flippase specificity for O-antigen diversity. The Wzx protein flips subunits of the polysaccharide O antigen (O-units) across the cell membrane on their way to the cell wall. The aim of this project is to determine the specificity that different Wzx flippases have for O unit structure. Previous research has shown that there is much more specificity than previously thought, making Wzx a very interesting protein. Wzx flippases vary enormously in sequence, presumably reflecting th ....Importance of Wzx flippase specificity for O-antigen diversity. The Wzx protein flips subunits of the polysaccharide O antigen (O-units) across the cell membrane on their way to the cell wall. The aim of this project is to determine the specificity that different Wzx flippases have for O unit structure. Previous research has shown that there is much more specificity than previously thought, making Wzx a very interesting protein. Wzx flippases vary enormously in sequence, presumably reflecting the diversity of sugars and linkages in O units. The significance lies in the role of these polysaccharides in interactions with the environment, including host-pathogen interactions and immune responses. The outcome will be a new understanding of the export specificity of O-antigens and also capsules, both of which make very good vaccines. Read moreRead less
Peril and promise: Origins and spread of integron gene cassettes. Integrons have a major role in spreading antibiotic resistance genes among pathogens. They do so by capturing gene cassettes encoding resistance, yet how these cassettes are generated, the taxa in which they originate, and the range of traits that cassettes can encode have been outstanding questions for 30 years. This project addresses these long standing questions. The project will analyze single bacterial cells to detect newly ....Peril and promise: Origins and spread of integron gene cassettes. Integrons have a major role in spreading antibiotic resistance genes among pathogens. They do so by capturing gene cassettes encoding resistance, yet how these cassettes are generated, the taxa in which they originate, and the range of traits that cassettes can encode have been outstanding questions for 30 years. This project addresses these long standing questions. The project will analyze single bacterial cells to detect newly generated cassettes and assign them to specific taxa, using an innovative method that links cassette DNA to bacterial 16S rDNA. Understanding cassette origins is the key to controlling their activity, both to harness integrons for biotechnology, and to prevent pathogens from acquiring new, dangerous traits. Read moreRead less
Genetics and evolution of Shigella O antigens. We use genome scale sequencing techniques to sequence 26 O-antigen gene clusters from Shigella. With the seven already known, this will give sequences for every O-antigen of Shigella. This will be the first time that such set is fully sequenced. Shigella are human specific pathogens, have emerged with the evolution of humans. O-antigens are important for their life and pathogenicity. This project will greatly extend our knowledge of the genetic basi ....Genetics and evolution of Shigella O antigens. We use genome scale sequencing techniques to sequence 26 O-antigen gene clusters from Shigella. With the seven already known, this will give sequences for every O-antigen of Shigella. This will be the first time that such set is fully sequenced. Shigella are human specific pathogens, have emerged with the evolution of humans. O-antigens are important for their life and pathogenicity. This project will greatly extend our knowledge of the genetic basis and evolution of this important polymorphism. O-antigens are used for typing Shigella and also elicit strong immunity. The molecular data will help establish DNA based typing and vaccine development.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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Structure function analysis of the NusA-RNA polymerase interaction. Genes must be turned on at the right time, at the correct level in the appropriate cell in all organisms. This project will determine the role of an essential component of the process in bacteria called NusA. The results will apply to bacteria as well as higher organisms, and also have the potential to identify a new antibiotic target.
Breaking through the Gram-negative cell barrier. This project aims to develop fundamental knowledge of the cell envelope in Gram-negative bacteria, which functions as a permeability barrier to small molecules. Combining innovative functional genomics with biochemistry, this project will determine how small molecules can pass across the cell envelope, and the chemical properties that they need to do so. Some Gram-negative bacteria are human pathogens and cause serious infections, whereas others a ....Breaking through the Gram-negative cell barrier. This project aims to develop fundamental knowledge of the cell envelope in Gram-negative bacteria, which functions as a permeability barrier to small molecules. Combining innovative functional genomics with biochemistry, this project will determine how small molecules can pass across the cell envelope, and the chemical properties that they need to do so. Some Gram-negative bacteria are human pathogens and cause serious infections, whereas others are used in biotechnology for biosynthetic chemical production or bioremediation. This project expects to help the future development of new antibiotics and assist in the design of strains to be used in biotechnological applications.Read moreRead less
Australian Laureate Fellowships - Grant ID: FL210100071
Funder
Australian Research Council
Funding Amount
$3,246,000.00
Summary
“L-form” bacteria: basic science, antibiotics, evolution and biotechnology. This Fellowship addresses key gaps in knowledge about cell wall deficient bacteria called L-forms: an altered state of bacteria with intriguing properties both structurally and functionally. The main aims of the research program are to improve our understanding of the basic biology of L-forms and employ them as tools in several important ways: for understanding the mechanisms of cell wall synthesis and how antibiotics wo ....“L-form” bacteria: basic science, antibiotics, evolution and biotechnology. This Fellowship addresses key gaps in knowledge about cell wall deficient bacteria called L-forms: an altered state of bacteria with intriguing properties both structurally and functionally. The main aims of the research program are to improve our understanding of the basic biology of L-forms and employ them as tools in several important ways: for understanding the mechanisms of cell wall synthesis and how antibiotics work, as models for early steps in the evolution of cellular life, and as a significant new platform for the production of proteins and fine chemicals. Outcomes and benefits include improved understanding of how to generate new antibiotics, and the development of new platforms for Australian biotechnology and biocommerce.Read moreRead less