Molecular characterisation of hypervirulence and the infectious cycle in Clostridium difficile. Gut diseases caused by the bacterium Clostridium difficile are a significant animal and public health problem in Australia and many other countries. This project will allow us to understand how this bacterium causes disease, leading to the development of much needed preventative and treatment strategies for animals and human patients.
The biology, structure and function of bacterial virulence effectors. This project is closely aligned with the National Research Priority of Promoting and Maintaining Good Health and will establish a research framework to investigate novel virulence processes that allow bacterial pathogens to infect humans and cause disease. This fresh approach to the study of bacterial pathogenesis will sit outside classic genetic methods to investigate infection and immunity which rely heavily on genetic manip ....The biology, structure and function of bacterial virulence effectors. This project is closely aligned with the National Research Priority of Promoting and Maintaining Good Health and will establish a research framework to investigate novel virulence processes that allow bacterial pathogens to infect humans and cause disease. This fresh approach to the study of bacterial pathogenesis will sit outside classic genetic methods to investigate infection and immunity which rely heavily on genetic manipulation of the pathogen. Other than providing fundamental information on host-pathogen interactions, this work may lead to novel disease interventions by inhibition of bacterial virulence factor activity and/or enhancement of host inflammatory and immune responses.Read moreRead less
Safety in numbers: Bacterial aggregation and adaptation to oxidative stress. This project is a new collaboration which links two molecular microbiologists with the complementary skills required to make new insights into the molecular processes that underpin bacterial aggregation and biofilm formation. Biofilms are of immense significance in medical, industrial and environmental settings and so the fundamental information gained from this project will have wider relevance to the field of microbio ....Safety in numbers: Bacterial aggregation and adaptation to oxidative stress. This project is a new collaboration which links two molecular microbiologists with the complementary skills required to make new insights into the molecular processes that underpin bacterial aggregation and biofilm formation. Biofilms are of immense significance in medical, industrial and environmental settings and so the fundamental information gained from this project will have wider relevance to the field of microbiology. An outcome of this proposal will be fundamental knowledge about the production of surface adhesins that will form the basis for rational treatment of disease in the future. Prevention of aggregation and biofilm formation would make bacterial populations more susceptible to conventional antibiotic treatment.Read moreRead less
Molecular mechanisms of pilin glycosylation in Neisseria: a model system for protein glycosylation in bacteria. The disease causing bacteria Neisseria meningitidis and Neisseria gonorrhoeae are important human pathogens. Cell surface structures, called pili, are known to be important in allowing the bacteria to stick to host cells. Genetic and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. Until recently ....Molecular mechanisms of pilin glycosylation in Neisseria: a model system for protein glycosylation in bacteria. The disease causing bacteria Neisseria meningitidis and Neisseria gonorrhoeae are important human pathogens. Cell surface structures, called pili, are known to be important in allowing the bacteria to stick to host cells. Genetic and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. Until recently glycosylation of Gram-negative bacterial proteins was not thought to occur, however our recent work with these bacteria, and other groups studying Pseudomonas and Campylobacter, have shown that this process may be widespread. In our previous studies, we have identified and analysed a number of genes involved in pili glycosylation, in bacteria, which make known sugar structures. We have used this information to developed models for how the biochemistry and physiology of the glycosylation system may work. With a well-established structure and many genes already identified, glycosylation in Neisseria represents the best available model system to study this novel and important process. In the proposed study we describe experiments planned to test our models and reveal the molecular detail of this process. This study could lead to major advances in our understanding of this process and, when understood, may have future applications in biotechnology.Read moreRead less
The host specificity of bacterial pathogens. The vast majority of microorganisms that cause diseases in animals are host specific. In other words, they cause disease exclusively in a particular animal species, but are harmless for others. Despite considerable recent advances in our understanding of the mechanisms used by microorganisms in general to cause disease, in most cases the underlying basis of host-specificity is not known. In this project, we will use two animal pathogens, rabbit-spe ....The host specificity of bacterial pathogens. The vast majority of microorganisms that cause diseases in animals are host specific. In other words, they cause disease exclusively in a particular animal species, but are harmless for others. Despite considerable recent advances in our understanding of the mechanisms used by microorganisms in general to cause disease, in most cases the underlying basis of host-specificity is not known. In this project, we will use two animal pathogens, rabbit-specific enteropathogenic E. coli and the closely related bacterium, Citrobacter rodentium, which specifically infect rabbits and mice respectively, to investigate the molecular basis of host specificity.Read moreRead less
The biology of integrons and their role in bacterial adaptation. Bacteria evolve in ways that animals and plants do not. One of the tools available is the ability to share genes amongst individuals in a community. One example of this is the very rapid spread of antibiotic resistance genes in pathogens. Here we will be studying a genetic element that greatly contributes to this horizontal spread of genes. This will lead to a better understanding of how bacteria work, the direct benefits of whic ....The biology of integrons and their role in bacterial adaptation. Bacteria evolve in ways that animals and plants do not. One of the tools available is the ability to share genes amongst individuals in a community. One example of this is the very rapid spread of antibiotic resistance genes in pathogens. Here we will be studying a genetic element that greatly contributes to this horizontal spread of genes. This will lead to a better understanding of how bacteria work, the direct benefits of which includes the discovery of new pathways and genes for the biotechnology industry and greater understanding of how bacteria cause disease in us, other animals and in commercial crops.Read moreRead less
A link between antibiotic resistance and bacterial sporulation. This project aims to define the sporulation process in the bacterium Clostridium difficile, and advance our understanding of a link between antibiotic use and sporulation. To survive in hostile environments, some bacteria produce a dormant and resilient cell form called a spore which can survive for many years in unfavourable environments, but our understanding of how this process occurs is limited. This project will provide a deepe ....A link between antibiotic resistance and bacterial sporulation. This project aims to define the sporulation process in the bacterium Clostridium difficile, and advance our understanding of a link between antibiotic use and sporulation. To survive in hostile environments, some bacteria produce a dormant and resilient cell form called a spore which can survive for many years in unfavourable environments, but our understanding of how this process occurs is limited. This project will provide a deeper understanding of the sporulation process and the long-lasting detrimental impact of antibiotic use. The project expects to provide economic benefits, reduce environmental microbial contamination and contribute to better health of animals and humans.Read moreRead less
A functional genomic approach for understanding metal ion adaptation in marine cyanobacteria. Unicellular marine cyanobacteria constitute 20-40% of total marine chlorophyll biomass and carbon fixation, and hence significantly impact the global carbon cycle and are very relevant to combating global warming. This research will reveal some of the major mechanisms by which marine cyanobacteria have adapted to metal levels in coastal and oligotrophic environments. Thus these results will help us und ....A functional genomic approach for understanding metal ion adaptation in marine cyanobacteria. Unicellular marine cyanobacteria constitute 20-40% of total marine chlorophyll biomass and carbon fixation, and hence significantly impact the global carbon cycle and are very relevant to combating global warming. This research will reveal some of the major mechanisms by which marine cyanobacteria have adapted to metal levels in coastal and oligotrophic environments. Thus these results will help us understand the distribution and diversity of these organisms in relation to global primary productivity. They will also lead to the development of more robust biomarkers for metal stress and pollution in coastal environments.Read moreRead less
Biology and evolution of intracellular parasitism. This project will investigate the development of intracellular parasitism in environmental amoebae. The outcomes of this work will help to understand the mechanisms by which bacteria have evolved to survive inside cells and in some cases cause disease.
Discovery Early Career Researcher Award - Grant ID: DE180101563
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
The sweet road to synthesis of bacterial sugar structures. This project aims to characterise the synthesis pathways of nonulosonic acid sugars (NulOs) in bacteria using a combination of bioinformatics and experimental methodologies. Bacteria produce long chains of sugars or glycans on their cell surface known as capsules. These often contain important NulOs that can be uniquely harvested for use in the nutrition, cosmetic and bioremediation industries. By understanding the natural pathways of th ....The sweet road to synthesis of bacterial sugar structures. This project aims to characterise the synthesis pathways of nonulosonic acid sugars (NulOs) in bacteria using a combination of bioinformatics and experimental methodologies. Bacteria produce long chains of sugars or glycans on their cell surface known as capsules. These often contain important NulOs that can be uniquely harvested for use in the nutrition, cosmetic and bioremediation industries. By understanding the natural pathways of their synthesis, ‘glycans-by-design’ can be synthetically created with potent tailor-made properties. This project endeavours to examine how glycans with acidic sugars are produced to generate a fundamental understanding of sugar biology and create a database that will advance industrial applications in glycoengineering.Read moreRead less