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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
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
EnzOnomy - an enzyme-based production pipeline for the bioeconomy. The sustainable production of high value chemicals (e.g. fuels, foods) from renewable materials is a cornerstone for the emerging global bioeconomy. We aim to harness the potential of protein engineering to develop a technology (EnzOnomy) to convert renewable raw material (e.g. sugar) into platform chemicals (e.g. isobutanol, a building block for jet fuels, fibers, plastics and antioxidants). Our multi-disciplinary and well estab ....EnzOnomy - an enzyme-based production pipeline for the bioeconomy. The sustainable production of high value chemicals (e.g. fuels, foods) from renewable materials is a cornerstone for the emerging global bioeconomy. We aim to harness the potential of protein engineering to develop a technology (EnzOnomy) to convert renewable raw material (e.g. sugar) into platform chemicals (e.g. isobutanol, a building block for jet fuels, fibers, plastics and antioxidants). Our multi-disciplinary and well established international team will link scientific progress to markets to enhance potential commercial impact in the bioeconomy. The project thus provides great benefit for our nation as it embeds Australia in technologies and global networks that will cement its leading position to safe-guard the future of our planet.
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Understanding the mechanisms of peptide cyclisation. This project aims to identify, study, engineer and apply a new class of biocatalysts (called asparaginyl endopeptidase enzymes) as versatile tools for manufacturing of advanced therapeutics and bio-insecticides. The expected outcomes include fundamental new knowledge on the mechanism of action of these catalysts, an expanded toolbox for precision engineering of biomolecules and new strategies for production of high-value pharmaceuticals and cr ....Understanding the mechanisms of peptide cyclisation. This project aims to identify, study, engineer and apply a new class of biocatalysts (called asparaginyl endopeptidase enzymes) as versatile tools for manufacturing of advanced therapeutics and bio-insecticides. The expected outcomes include fundamental new knowledge on the mechanism of action of these catalysts, an expanded toolbox for precision engineering of biomolecules and new strategies for production of high-value pharmaceuticals and crop protecting agents. The project is significant because it will contribute to high value biotechnology and agricultural industries in Australia, with the potential for economic, environmental, training and societal benefits.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
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
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
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
Understanding chaperone function, one molecule at a time. This project aims to determine how molecular chaperones, a class of proteins represented in all phyla of life, work together to keep proteins folded and functional, particularly following cellular stress. This is important as proteins are involved in virtually all biological processes. This project will exploit innovative microscopy techniques to watch these molecular chaperones as they work. Expected outcomes of this project are the firs ....Understanding chaperone function, one molecule at a time. This project aims to determine how molecular chaperones, a class of proteins represented in all phyla of life, work together to keep proteins folded and functional, particularly following cellular stress. This is important as proteins are involved in virtually all biological processes. This project will exploit innovative microscopy techniques to watch these molecular chaperones as they work. Expected outcomes of this project are the first definitive description of how molecular chaperones interact to refold proteins, and the development of novel methods to study dynamic biological processes. This should provide significant benefits including enhanced collaboration and scientific capacity in Australia.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