Molecular mechanisms of novel bacterial copper defense proteins. This project aims to reveal molecular and cellular mechanisms used by bacteria to neutralise the destructive effects of copper. Copper is an essential trace element in living systems. It is toxic to bacteria and so plays a vital role in nutritional immunity. To counteract copper toxicity, bacteria have evolved defense mechanisms. The project will investigate a novel but poorly understood class of bacterial proteins, the suppressor ....Molecular mechanisms of novel bacterial copper defense proteins. This project aims to reveal molecular and cellular mechanisms used by bacteria to neutralise the destructive effects of copper. Copper is an essential trace element in living systems. It is toxic to bacteria and so plays a vital role in nutritional immunity. To counteract copper toxicity, bacteria have evolved defense mechanisms. The project will investigate a novel but poorly understood class of bacterial proteins, the suppressor of copper sensitivity proteins, that contribute to this key virulence trait. The expected outcomes will be fundamental new knowledge of metallo-protein diversity, bacterial virulence mechanisms, and membrane protein function with potential impact on health, environment, and biotechnology.Read moreRead less
Understanding the structural basis for catalysis and substrate specificity in non-heme diiron medium-chain alkane hydroxylases. This work will determine the molecular basis for catalysis and specificity of non-heme diiron medium-chain alkane hydroxylases by obtaining the first structure of such an enzyme. This pivotal knowledge will drive enzyme engineering for applications in biodegradation of spilt oils and biosynthesis of pharmaceuticals and high-cost chemicals.
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100078
Funder
Australian Research Council
Funding Amount
$500,000.00
Summary
Establishment of a comprehensive regional biophysical analysis facility. Interactions between molecules are needed for cells to function correctly. This facility will permit comprehensive molecular characterisation as well as research into the fundamentals of how molecules interact.
Structures to Solve Conflicts of DNA Replication and RNA Transcription. This project aims to understand how new DNA is made so quickly and without mistakes in cells that are about to divide, in spite of competition from other processes happening at the same time on the DNA that should stop or interfere with it, such as the synthesis of RNA. The project expects to use the latest available methods to uncover what the microscopic natural machines that make DNA and RNA look like, and how they compet ....Structures to Solve Conflicts of DNA Replication and RNA Transcription. This project aims to understand how new DNA is made so quickly and without mistakes in cells that are about to divide, in spite of competition from other processes happening at the same time on the DNA that should stop or interfere with it, such as the synthesis of RNA. The project expects to use the latest available methods to uncover what the microscopic natural machines that make DNA and RNA look like, and how they compete with each other for access to DNA. Potential outcomes include the identification of processes that can be compromised by small molecules that may be developed into new antibiotics. This would be of great benefit - new antibiotics are urgently needed as one approach to countering the threat of antimicrobial resistance.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE140100096
Funder
Australian Research Council
Funding Amount
$180,000.00
Summary
Biomolecular Interaction Facility. Biomolecular interaction facility: A biomolecular interaction facility located in Perth is essential to support the research performed by a growing community of key protein researchers. The infrastructure provided by this integrated facility will act as a hub for analysis of samples produced by high-throughput protein production methods and will provide high-level training with cutting-edge equipment for researchers at all levels. It will underpin faster and be ....Biomolecular Interaction Facility. Biomolecular interaction facility: A biomolecular interaction facility located in Perth is essential to support the research performed by a growing community of key protein researchers. The infrastructure provided by this integrated facility will act as a hub for analysis of samples produced by high-throughput protein production methods and will provide high-level training with cutting-edge equipment for researchers at all levels. It will underpin faster and better fundamental and translational research in the areas of structural biology, biotechnology, biomedical science, plant science and nanotechnology, supporting the activities of researchers and their collaborators in Australia and worldwide.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
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.
Roadblocks in DNA replication. This project aims to develop the technology to visualise and understand the molecular processes responsible for the faithful copying of cellular DNA in the presence of roadblocks caused by chemical pressures and competing intracellular events. Understanding this process is important as DNA replication is responsible for copying the DNA genetic blueprint of cells and is crucial to all life on earth. This project will have as key outcomes the development of novel mol ....Roadblocks in DNA replication. This project aims to develop the technology to visualise and understand the molecular processes responsible for the faithful copying of cellular DNA in the presence of roadblocks caused by chemical pressures and competing intracellular events. Understanding this process is important as DNA replication is responsible for copying the DNA genetic blueprint of cells and is crucial to all life on earth. This project will have as key outcomes the development of novel molecular visualisation technology and the first molecular description of the dynamic processes used by the DNA-replication machinery to navigate roadblocks. These outcomes should provide significant benefits including enhanced collaboration and scientific capacity in Australia.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100171
Funder
Australian Research Council
Funding Amount
$200,000.00
Summary
Shared resource for protein discovery. This facility will enable the production and characterisation of proteins from all kingdoms of life that have diverse roles in fundamental biology and disease. A detailed understanding of how these proteins behave and function will be used to generate therapeutics and develop novel applications for these proteins in medicine and industry.