Phase-variable epigenetic regulators in bacterial veterinary pathogens. This project aims to identify phasevarion regulated genes in the major bacterial swine pathogens Streptococcus suis and Actinobacillus pleuropneumoniae. Both species contain randomly switching epigenetic regulators that control expression of multiple genes by epigenetic mechanisms. Identifying phasevarion controlled genes will inform and direct future vaccine development for important livestock species.
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
YhcB, a crucial player in the control of bacterial cell envelope biogenesis. All life depends on a cell envelope to enclose the chemical reactions that make life possible. But how do cell envelopes grow? How each component of the cell envelope is incorporated into the envelope at the right amount and in the right time to prevent cell death, has been a longstanding question in bacteriology. Using a unique combination of high through put genetic screens and biochemical approaches, this project wil ....YhcB, a crucial player in the control of bacterial cell envelope biogenesis. All life depends on a cell envelope to enclose the chemical reactions that make life possible. But how do cell envelopes grow? How each component of the cell envelope is incorporated into the envelope at the right amount and in the right time to prevent cell death, has been a longstanding question in bacteriology. Using a unique combination of high through put genetic screens and biochemical approaches, this project will characterise a key regulator of cell envelope growth in Gram-negative bacteria. Knowledge arising from this research will provide insight into a fundamental process in bacteria, will develop new technology to probe protein interactions, and will provide novel avenues to solve infection in plants, humans and animals.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
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
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
Evolution of bacterial pathogenesis. Little is known regarding the specific evolutionary steps involved in the emergence of highly virulent microbial pathogens from benign or mildly virulent populations. The group A streptococcus is exemplary of this vexing problem - a large population reservoir of bacteria exists causing only mild infections and a highly virulent strain emerges causing significant disease and mortality. Utilising an extensive WHO reference collection of group A streptococcus is ....Evolution of bacterial pathogenesis. Little is known regarding the specific evolutionary steps involved in the emergence of highly virulent microbial pathogens from benign or mildly virulent populations. The group A streptococcus is exemplary of this vexing problem - a large population reservoir of bacteria exists causing only mild infections and a highly virulent strain emerges causing significant disease and mortality. Utilising an extensive WHO reference collection of group A streptococcus isolates. This project will define the evolutionary events that produced the most significant invasive strain designated M1T1. The M1T1 strain emerged in the mid-1980s, has since disseminated globally, yet the evolutionary sequence of events resulting in this emergence are largely unknown.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
The protein O-glycosylation pathway in Neisseria meningitidis. Neisseria meningitidis causes bacterial meningitis, a sudden and severe disease of particular concern to children in both the developed and developing worlds. This project will contribute to an understanding of how these bacteria evade the immune system by modifying the proteins displayed on their surface, which will help in the development of a vaccine.
The molecular mechanism of action of bacterial epigenetic regulators. This project aims to determine the mechanisms of action of a class of bacterial epigenetic regulators. Many bacteria exhibit phase variable expression of genes (random, high frequency on/off switching of expression), typically due to simple DNA repeats within the gene(s) that encode them. Many bacterial species contain phase variable DNA methyltransferases that regulate epigenetics and control expression of distinct sets of pr ....The molecular mechanism of action of bacterial epigenetic regulators. This project aims to determine the mechanisms of action of a class of bacterial epigenetic regulators. Many bacteria exhibit phase variable expression of genes (random, high frequency on/off switching of expression), typically due to simple DNA repeats within the gene(s) that encode them. Many bacterial species contain phase variable DNA methyltransferases that regulate epigenetics and control expression of distinct sets of proteins (phasevarions) via variable methylation of the genome. The precise mechanism of action of these regulators is unknown. Characterisation of these systems will provide better understanding of bacterial gene regulation and adaptation, which will inform biotechnology and vaccine development and could contribute to economic and health advancements.Read moreRead less