Linking immunomodulation and latency in alphaherpesvirus infection. Herpesviruses cause major diseases in humans and all domestic animal species. Latency forms a significant part of the evolutionary success of herpesviruses, by enabling transmission of the virus throughout the lifetime of the host. Our work has shown that an alphaherpesvirus protein can divert the host’s immune response to become more antibody-mediated and less T cell-mediated. This study explores the consequences of this immune ....Linking immunomodulation and latency in alphaherpesvirus infection. Herpesviruses cause major diseases in humans and all domestic animal species. Latency forms a significant part of the evolutionary success of herpesviruses, by enabling transmission of the virus throughout the lifetime of the host. Our work has shown that an alphaherpesvirus protein can divert the host’s immune response to become more antibody-mediated and less T cell-mediated. This study explores the consequences of this immune diversion, and examines whether this reduced T cell response enables the development of latent infections. Disrupting the virus-host balance by alterations to this conserved viral protein will enable novel approaches to controlling these economically significant viruses.Read moreRead less
The development and evaluation of a new therapy for the prevention and treatment of bacterial infections in hospitals. The technology used in this project will enable products to be developed from the Australian dairy industry which may safely provide protection and treatment for diarrhoea acquired in hospitals for which there are few effective options. The product will be cost effective and can be used as a public health tool to control outbreaks in those most susceptible to severe disease.
Transport and innate immune properties of DNA in bacterial nano-sized vesicles. All types of living organisms release nano-sized membrane vesicles or “blebs” which they use for intercellular communication and transport of molecules. This project will determine how bacteria package DNA within these vesicles, how this DNA is transported into host cells and how it triggers immune responses in these cells.
Host-pathogen interactions: the role of mimicry. The proposed research program, using a combination of structure and functional analysis will provide insight into the mechanism of nucleotide hydrolysis by the enzymes NTPDases. This study will not only improve our fundamental understanding of NTPDase action but could lead to the rational design of antimicrobials.
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.
Investigation of a Novel Protein Implicated in Phosphate Metabolism in Bacteria. Phosphate is an important nutrient for all forms of life on Earth. A novel bacterial protein has been identified that appears to be important for the uptake or processing of phosphate, since mutants lacking the protein grow poorly inside certain cells of the human immune system (where phosphate levels are low) and in media containing low phosphate. The aims of this project are: to determine the role of the protein b ....Investigation of a Novel Protein Implicated in Phosphate Metabolism in Bacteria. Phosphate is an important nutrient for all forms of life on Earth. A novel bacterial protein has been identified that appears to be important for the uptake or processing of phosphate, since mutants lacking the protein grow poorly inside certain cells of the human immune system (where phosphate levels are low) and in media containing low phosphate. The aims of this project are: to determine the role of the protein by examining all phosphate containing molecules in our mutants; to determine its location in bacteria and functional domains; to identify other affected genes in our mutants; and, to find proteins that interact with this new protein. This project expects to demonstrate the importance of this protein in phosphate metabolism in bacteria.Read moreRead less
Molecular basis of attenuation in live Mycoplasma vaccines. This proposal aims to use an innovative approach to address an urgent issue raised by the end users of an Australian-owned poultry vaccine with an extensive global market. Recently multiple mutations have been detected in the vaccine re-isolated from vaccinated birds in the field around the world. We will apply a combination of a novel technique for targeted mutagenesis, genome sequencing, and animal experimentations, to address the sig ....Molecular basis of attenuation in live Mycoplasma vaccines. This proposal aims to use an innovative approach to address an urgent issue raised by the end users of an Australian-owned poultry vaccine with an extensive global market. Recently multiple mutations have been detected in the vaccine re-isolated from vaccinated birds in the field around the world. We will apply a combination of a novel technique for targeted mutagenesis, genome sequencing, and animal experimentations, to address the significance of these mutations. Results will improve our understanding of the basis of attenuation of the vaccine, its mechanism of action, and provide commercial confidence in the safety of the vaccine, which is needed to support Australian Universities and Businesses, and the global poultry industry.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120101340
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Subversion of innate immune responses by pathogenic Escherichia coli. This project will determine how bacteria that cause diarrhoeal diseases prevent the immune system from signalling efficiently. It will provide important information not only about how the bacteria establish disease, but also provide insight into the host response in the early stages of infection.
How Bacteria Fold Virulence Factors to Cause Disease. Bacteria use folding enzymes to assemble proteins essential for cell integrity and pathogenicity. These foldases include the Disulphide bridge proteins, which catalyse the introduction of disulfide bonds. This project will study two important human pathogens, Salmonella Typhimurium and uropathogenic Escherichia coli, to address the fundamental and poorly understood questions of diversity of Dsb networks across bacterial pathogens and the role ....How Bacteria Fold Virulence Factors to Cause Disease. Bacteria use folding enzymes to assemble proteins essential for cell integrity and pathogenicity. These foldases include the Disulphide bridge proteins, which catalyse the introduction of disulfide bonds. This project will study two important human pathogens, Salmonella Typhimurium and uropathogenic Escherichia coli, to address the fundamental and poorly understood questions of diversity of Dsb networks across bacterial pathogens and the role of these foldases in virulence. The research will reveal how bacterial virulence factors are folded, identify novel targets for therapeutic intervention and provide the basis for structure-based design on new antimicrobials in the future. Read moreRead less
Unraveling autotransporter function in bacterial aggregates and biofilms. Autotransporters are a large family of bacterial proteins that play a central role in pathogenesis. They promote the formation of cell clusters and biofilms, which are mechanisms for bacterial resistance to host immune factors and antibiotics. Currently, the precise mode of action of autotransporters is unknown. This project will examine the interplay between the structure and function of key autotransporter proteins. It ....Unraveling autotransporter function in bacterial aggregates and biofilms. Autotransporters are a large family of bacterial proteins that play a central role in pathogenesis. They promote the formation of cell clusters and biofilms, which are mechanisms for bacterial resistance to host immune factors and antibiotics. Currently, the precise mode of action of autotransporters is unknown. This project will examine the interplay between the structure and function of key autotransporter proteins. It is expected that the outcomes of this research will establish how these proteins mediate aggregation and biofilm formation. It may also provide three-dimensional structures of proteins that are strongly immunogenic and may represent targets for future vaccine design, as well as identify molecules that inhibit autotransporter function.Read moreRead less