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
Discovery Early Career Researcher Award - Grant ID: DE190100304
Funder
Australian Research Council
Funding Amount
$416,092.00
Summary
Understanding intramolecular regulation of ubiquitin enzymes. This project aims to combine structural, biophysical and functional studies to characterise how ubiquitin enzymes are regulated. Ubiquitination controls essential cellular pathways in all eukaryotes and this project expects to generate new knowledge regarding the vital regulation of this process. This project expects to develop broadly applicable techniques for investigating protein conformation and self-association as a means of cont ....Understanding intramolecular regulation of ubiquitin enzymes. This project aims to combine structural, biophysical and functional studies to characterise how ubiquitin enzymes are regulated. Ubiquitination controls essential cellular pathways in all eukaryotes and this project expects to generate new knowledge regarding the vital regulation of this process. This project expects to develop broadly applicable techniques for investigating protein conformation and self-association as a means of controlling catalytic activity. The project should significantly increase understanding of several modes of regulation of ubiquitin ligase catalytic activity, and how this controls a myriad of cellular processes. The project will lay the foundation for applied research anti-viral compounds, plant anti-fungals and cancer therapies.Read moreRead less
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
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.
Structural and functional characterisation of compounds that inhibit the malarial aminopeptidases. Malaria is the world's most prevalent parasitic disease. Due to the rapid spread of drug resistant parasites there is a need to develop new antimalarial drugs. In this proposal we will characterise new targets and novel methods of inhibition that will form the basis of a new mechanism for antimalarial drugs.
The regulation of anti-viral immunity by host and viral proteins. Anti-viral immunity is initially triggered when specific immune sensors detect viral components within the cell. This project will use a combined functional/structural approach to investigate the specifics of immune activation by a pivotal immune sensor and use this information to understand how influenza A sabotages this specific immune response.
Structural and functional analysis of the protein kinase R. We have shown that protein kinase R (PKR) plays a key role in regulating the body's response to virus infections, inflammation and cancer. This project will identify mechanisms that regulate the activity of PKR and provide information useful for the development of novel drugs.