Metals in biocatalysis. Metals and enzymes are essential for the chemistry of life. This project will aim to garner the potential of metal-dependent enzymes to develop new drugs against osteoporosis, combat the spread of antibiotics resistance and optimise some of these enzymes to detoxify pesticide-polluted environments, thus contributing to global health and food security.
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
Resurrecting Ancient Proteins to Unlock New Catalytic Activity. This project aims to study the proteins that nature uses to make penicillin and related antibiotics, and their prehistoric ancestors. By doing so, the project expects to deepen understanding of these important processes, open up ways to make new antibiotics, and generate new knowledge about protein evolution. Intended outcomes include new biocatalysts based on the ancient ones, new antibiotic compounds active against resistant bacte ....Resurrecting Ancient Proteins to Unlock New Catalytic Activity. This project aims to study the proteins that nature uses to make penicillin and related antibiotics, and their prehistoric ancestors. By doing so, the project expects to deepen understanding of these important processes, open up ways to make new antibiotics, and generate new knowledge about protein evolution. Intended outcomes include new biocatalysts based on the ancient ones, new antibiotic compounds active against resistant bacteria, and a richer understanding of how these proteins have evolved over the last 4 billion years. This promises significant benefits in the form of new ways to address the challenge posed by antimicrobial resistance to antibiotics, which is a serious threat to the continued effectiveness of current antibiotics.Read moreRead less
Unlocking the secret chemistry of organosulfur biodegradation. The element sulfur is essential for life. Its transformation between organic-sulfur compounds to inorganic forms is a crucial part of the biogeochemical cycle. This project will elucidate the molecular details of the final leg of the biosulfur cycle: organosulfur breakdown into mineral form. An integrated chemical and biochemical approach will be used to illuminate how the carbon-sulfur bond is broken. This project will deliver a det ....Unlocking the secret chemistry of organosulfur biodegradation. The element sulfur is essential for life. Its transformation between organic-sulfur compounds to inorganic forms is a crucial part of the biogeochemical cycle. This project will elucidate the molecular details of the final leg of the biosulfur cycle: organosulfur breakdown into mineral form. An integrated chemical and biochemical approach will be used to illuminate how the carbon-sulfur bond is broken. This project will deliver a detailed molecular understanding of organosulfur breakdown to permit organosulfur recycling. Benefits of this research include potential biotechnology applications for breaking down xenobiotic organosulfonates and sustainable approaches to reduce dependence on agricultural fertilisers.Read moreRead less
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
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
Electron transport catalysis in organohalide pollutant respiration. This project aims to understand the link between substrate specificity and gene sequence of dehalogenating enzymes in organohalide respiring bacteria (ORB) and the mechanism by which electrons are transferred to dehalogenating enzymes through protein-protein interactions. Organohalides were present in Earth's early history and now pollute the environment globally. Organohalide respiring bacteria (ORB) can degrade these pollutant ....Electron transport catalysis in organohalide pollutant respiration. This project aims to understand the link between substrate specificity and gene sequence of dehalogenating enzymes in organohalide respiring bacteria (ORB) and the mechanism by which electrons are transferred to dehalogenating enzymes through protein-protein interactions. Organohalides were present in Earth's early history and now pollute the environment globally. Organohalide respiring bacteria (ORB) can degrade these pollutants by using them as terminal electron acceptors in their respiratory metabolism. This represents one of the most ancient respiratory systems on Earth about which little is known. This project will add to our fundamental knowledge of microbial evolution and metabolic systems, and pave the way for next generation organohalide remediation technologies.Read moreRead less
Unveiling and characterisation of a fundamental pathway important in cell division. This work will have a major impact by producing top quality research that addresses a fundamental biological question of relevance to all organisms. The research will advance understanding of genetic factors important in foetal and early childhood development and proliferative disorders that occur during ageing. This work will provide intellectual and practical training to Honours and PhD students and postdoctora ....Unveiling and characterisation of a fundamental pathway important in cell division. This work will have a major impact by producing top quality research that addresses a fundamental biological question of relevance to all organisms. The research will advance understanding of genetic factors important in foetal and early childhood development and proliferative disorders that occur during ageing. This work will provide intellectual and practical training to Honours and PhD students and postdoctoral researchers in the disciplines of Molecular Genetics, Molecular & Cellular Biology, Developmental Cell Biology, Mass Spectrometry and Proteomics, which will be of immense benefit to their scientific careers and the Australian scientific community.Read moreRead less
A microbiological platform for the production of complex small molecules with important biological activities. Currently making complex chemicals such as medicines relies on harvesting rare natural resources or using complicated, energy intensive laboratory-based processes. This project will overcome these limitations by using a natural biological system to produce these chemicals, returning significant health and economic benefits to the nation.
Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. ....Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. Knowledge about this new aspect of protein degradation could provide a powerful tool to test the effect of the stabilisation or removal of specific proteins in the cell and also to develop new technologies in protein production.Read moreRead less