Augmenting the activity of glyoxalase-1 to increase dicarbonyl clearance . Reactive intermediates generated during our metabolism contribute to ageing. Glyoxalase-1 is a key defence enzyme against these toxic intermediates and therefore ageing itself. This project aims to investigate novel pathways how the expression and activity of glyoxalase-1 are regulated. This interdisciplinary project expects to generate new understanding by combining relevant cell and animal models, protein chemistry, epi ....Augmenting the activity of glyoxalase-1 to increase dicarbonyl clearance . Reactive intermediates generated during our metabolism contribute to ageing. Glyoxalase-1 is a key defence enzyme against these toxic intermediates and therefore ageing itself. This project aims to investigate novel pathways how the expression and activity of glyoxalase-1 are regulated. This interdisciplinary project expects to generate new understanding by combining relevant cell and animal models, protein chemistry, epigenetics and structural biology. It is expected that this work will improve understanding of this fundamental biological defence. This will allow us to identify the potential means to enhance the capacity of glyoxalase-1 to the future benefit of biological ageing.Read moreRead less
Regulation of autophagy dependent cell and tissue deletion. This project aims to elucidate novel mechanisms that regulate autophagy-depdendent cell death during animal development. It will combine the power of Drosophila genetics with multidisciplinary approaches, such as proteomics, bioinformatics and cell biology. Given the conserved nature of autophagy the oucomes will provide highly topical and exciting new knowledge of broad biological significance. The project will help establishing inter ....Regulation of autophagy dependent cell and tissue deletion. This project aims to elucidate novel mechanisms that regulate autophagy-depdendent cell death during animal development. It will combine the power of Drosophila genetics with multidisciplinary approaches, such as proteomics, bioinformatics and cell biology. Given the conserved nature of autophagy the oucomes will provide highly topical and exciting new knowledge of broad biological significance. The project will help establishing international collaborations, enhancing Australia’s competitiveness and reputation in an important area of research, and provide training of HDR students in skills across a range of areas. In the long-term the research findings may translate into improved agriculture, food production and human health outcomes.Read moreRead less
Re-purposing shelved 'antibiotics' in the search for new herbicides. This project aims to identify target-specific herbicidal compounds that inhibit amino acid biosynthesis pathways to tackle herbicide resistance. This project expects to validate a novel herbicide discovery strategy by exploiting the similarity between bacterial and plant enzymes in these pathways to re-purpose failed 'antibiotics'. Expected outcomes include advances in our knowledge of the structure, function and inhibition of ....Re-purposing shelved 'antibiotics' in the search for new herbicides. This project aims to identify target-specific herbicidal compounds that inhibit amino acid biosynthesis pathways to tackle herbicide resistance. This project expects to validate a novel herbicide discovery strategy by exploiting the similarity between bacterial and plant enzymes in these pathways to re-purpose failed 'antibiotics'. Expected outcomes include advances in our knowledge of the structure, function and inhibition of novel herbicide targets, and the identification of compounds with herbicidal activity. This should lay the foundations for long-term benefits related to improving the quantity and quality of Australia’s crops to ensure our food security.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100418
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Novel chemical tools to study cathepsin X activation. This project aims to develop new chemical tools that can measure the specific activation of cathepsin X in cells, tissues, and live animals, as well as specific inhibitors for cathepsin X. The cysteine protease cathepsin X mediates basic biological functions that are essential for life, including cell communication, phagocytosis, immune maturation and neuritogenesis. The outcomes should benefit the wider research community. They could have lo ....Novel chemical tools to study cathepsin X activation. This project aims to develop new chemical tools that can measure the specific activation of cathepsin X in cells, tissues, and live animals, as well as specific inhibitors for cathepsin X. The cysteine protease cathepsin X mediates basic biological functions that are essential for life, including cell communication, phagocytosis, immune maturation and neuritogenesis. The outcomes should benefit the wider research community. They could have long-term implications for health and disease, and deliver economic benefits through commercialisation of the novel tools.Read moreRead less
Extracting energy from air: mechanism of a bacterial hydrogenase. The atmosphere has recently been shown to be a key source of energy for diverse soil bacteria. Bacteria use complex enzymes, namely Huc-type hydrogenases, to harvest atmospheric hydrogen directly from air to support growth and survival. However, little is known about how Huc functions within and outside cells. By synergising expertise in microbiology, biochemistry, and chemistry, we will resolve the mechanism, assembly, and integr ....Extracting energy from air: mechanism of a bacterial hydrogenase. The atmosphere has recently been shown to be a key source of energy for diverse soil bacteria. Bacteria use complex enzymes, namely Huc-type hydrogenases, to harvest atmospheric hydrogen directly from air to support growth and survival. However, little is known about how Huc functions within and outside cells. By synergising expertise in microbiology, biochemistry, and chemistry, we will resolve the mechanism, assembly, and integration of Huc, including the basis of its remarkably high affinity and oxygen insensitivity compared to previously studied hydrogenases. This project will enable biotechnological applications, as the first study of an enzyme that extracts energy from air, and has broad ecological and biogeochemical implications.Read moreRead less
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
Discovery Early Career Researcher Award - Grant ID: DE230101173
Funder
Australian Research Council
Funding Amount
$374,318.00
Summary
Inhibiting adenylate-forming enzymes via a new reaction-hijacking mechanism. This project aims to identify and validate the adenylate-forming enzymes that are susceptible to reaction-hijacking inhibition in malaria parasites. This class of enzymes can be induced to synthesise their own nucleoside sulfamate inhibitor conjugates via a novel mechanism. This project expects to provide new knowledge about the molecular basis of this novel inhibition mechanism and susceptible target enzymes in the par ....Inhibiting adenylate-forming enzymes via a new reaction-hijacking mechanism. This project aims to identify and validate the adenylate-forming enzymes that are susceptible to reaction-hijacking inhibition in malaria parasites. This class of enzymes can be induced to synthesise their own nucleoside sulfamate inhibitor conjugates via a novel mechanism. This project expects to provide new knowledge about the molecular basis of this novel inhibition mechanism and susceptible target enzymes in the parasites. Adenylate-forming enzymes play critical roles in a diverse range of biochemical pathways, such as protein translation and fatty acid metabolism. The project seeks to deliver a new paradigm for the design of future antiparasitic agents.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190100806
Funder
Australian Research Council
Funding Amount
$419,854.00
Summary
Towards herbicide cocktails with a new mode of action to avert resistance. This project aims to target herbicide resistant weeds which represent one of the largest threats to Australian and global food security. Targeting of unexplored pathways in plants to develop a novel herbicide strategy is expected to be achieved, and will include the structural and functional characterisation of key enzymes in these pathways. This project is expected to provide significant benefits for effective weed manag ....Towards herbicide cocktails with a new mode of action to avert resistance. This project aims to target herbicide resistant weeds which represent one of the largest threats to Australian and global food security. Targeting of unexplored pathways in plants to develop a novel herbicide strategy is expected to be achieved, and will include the structural and functional characterisation of key enzymes in these pathways. This project is expected to provide significant benefits for effective weed management to sustain Australia’s agricultural industry through enhanced food production from increased crop yields, whilst ensuring food security. These outcomes, coupled with decades of over-reliance on current herbicides, means there has never been a greater need for new and effective herbicides.Read moreRead less