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Mid-Career Industry Fellowships - Grant ID: IM230100534
Funder
Australian Research Council
Funding Amount
$874,096.00
Summary
NOVEL MASS-SCALE BIOSYNTHESIS: TAILORING CHEMICAL LOGIC & BIOSYNTHESIS. No new antibiotics against Gram-negative ‘superbugs’ are expected to be available in the near future. We have exhausted the chemical space from the natural product pool and lack a fundamental understanding of antibiotics in nature, this is a major hurdle for antibiotic design targeting bacterial resistance. This proposal aims to engineer unique chemo-enzymatic platforms for the synthesis of new lipopeptide scaffolds which wi ....NOVEL MASS-SCALE BIOSYNTHESIS: TAILORING CHEMICAL LOGIC & BIOSYNTHESIS. No new antibiotics against Gram-negative ‘superbugs’ are expected to be available in the near future. We have exhausted the chemical space from the natural product pool and lack a fundamental understanding of antibiotics in nature, this is a major hurdle for antibiotic design targeting bacterial resistance. This proposal aims to engineer unique chemo-enzymatic platforms for the synthesis of new lipopeptide scaffolds which will significantly expand the chemical space available for novel antibiotic discovery. The development of these unique platforms will greatly expand our inventory of natural product antibiotics and will represent a major technological break-through for Australia's biotechnology and pharmaceutical manufacturing sectors.Read moreRead less
Escaping Bio-Assay Guided Isolation: Nature's Tools for Chemical Biology. The project aims to transform the approach to identify novel biologically active compounds that occur in nature. For decades, natural product chemistry has centred on bio-assay guided isolation, but it has become increasingly difficult to isolate novel compounds. While de-replication strategies detect the presence of known compounds using databases, more impact would be achieved by directly detecting novel compounds. Nucle ....Escaping Bio-Assay Guided Isolation: Nature's Tools for Chemical Biology. The project aims to transform the approach to identify novel biologically active compounds that occur in nature. For decades, natural product chemistry has centred on bio-assay guided isolation, but it has become increasingly difficult to isolate novel compounds. While de-replication strategies detect the presence of known compounds using databases, more impact would be achieved by directly detecting novel compounds. Nuclear magnetic resonance (NMR) spectroscopy detects every molecule that has a proton and is quantitative. This project plans to develop a NMR technique to escape bio-assay guided isolation by analysing a fraction library. Biotechnology innovation is dependent on novel compounds to provide new products. Replacing ‘grind and find’ with a technique that never lies would be transformational.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100170
Funder
Australian Research Council
Funding Amount
$580,000.00
Summary
Bioaffinity mass spectrometry infrastructure to identify small molecules binding to therapeutic targets. The development of anti-infective therapies is challenging because the underlying biology and biochemistry of pathogen virulence is not yet completely understood. This mass spectrometer facility will be used to identify small molecules suited for development into new therapies for malaria, tuberculosis and HIV.
Towards an influenza virus glycan interaction map (Glycointeractome). This project will use nuclear magnetic resonance (NMR) spectroscopy to map carbohydrate interaction used by the virus to cause infection and spread. This information will provide new direction in anti-influenza drug discovery.
Novel chemoenzymatic synthesis and bioconjugation of peptides and proteins. This project aims to solve the critical difficulty of producing the complex peptide insulin and related insulin-like peptides (INSLs) and their analogues. The project will use unique, recyclable enzymes which ligate smaller peptide segments with extraordinary site and substrate selectivity. The expected outcome of the project is novel, cheaper and scalable, enzyme-mediated engineering of this critical class of peptides a ....Novel chemoenzymatic synthesis and bioconjugation of peptides and proteins. This project aims to solve the critical difficulty of producing the complex peptide insulin and related insulin-like peptides (INSLs) and their analogues. The project will use unique, recyclable enzymes which ligate smaller peptide segments with extraordinary site and substrate selectivity. The expected outcome of the project is novel, cheaper and scalable, enzyme-mediated engineering of this critical class of peptides as biological probes and potential therapeutic agents.Read moreRead less
Chemical probes for visualising DNA synthesis. This project aims to develop chemical probes to quantify DNA synthesis in complex mammalian and parasite cellular systems in conjunction with image-based technologies. Chemical probes are small molecule reagents that have a profound impact on our ability to answer fundamental questions about biological processes within living cells. The probes will be differentiated from current probes that are toxic or incompatible with state-of-the art imaging. Th ....Chemical probes for visualising DNA synthesis. This project aims to develop chemical probes to quantify DNA synthesis in complex mammalian and parasite cellular systems in conjunction with image-based technologies. Chemical probes are small molecule reagents that have a profound impact on our ability to answer fundamental questions about biological processes within living cells. The probes will be differentiated from current probes that are toxic or incompatible with state-of-the art imaging. The project expects to generate intellectual property with potential for development into commercial products that allow researchers expanded opportunities to study complex biological processes.Read moreRead less
Inhibition of membrane-bound carbonic anhydrases with small molecules as a novel approach to target a safe and effective treatment for solid tumours. Over 85 per cent of human cancers are solid tumours and the prognosis for patients with advanced solid tumours is extremely poor owing to resistance to conventional chemo- and radio- therapies. Our research will underpin the development of new, safe and effective drug treatment options for cancer patients with solid tumours.
Lymphotropic prodrugs: a novel mechanism for targeted drug delivery. This project aims to design chemically modified drugs that target drug delivery specifically to white blood cells. This approach promises to maximise drug action and simultaneously reduce toxicity for diseases where lymphocytes are the major drug target. These include autoimmune disease, leukaemia, lymphoma, HIV, transplant rejection and diabetes.
Understanding allosteric modulation and functional selectivity at G Protein-Coupled Receptors (GPCRs). GPCRs are an important superfamily of proteins that are involved in a myriad of physiological processes and a wide range of serious illnesses. This project seeks to gain a more detailed understanding of new mechanisms of GPCR modulation and function that will be of direct relevance to drug discovery.
Subtype selectivity and functional bias of receptor positive allosteric modulators for understanding models of pulmonary disease. G-protein-coupled receptors (GPCRs) are an important superfamily of proteins that are involved in a myriad of physiological processes and a wide range of serious illnesses. This project seeks to gain a more detailed understanding of new mechanisms of GPCR modulation and function that will be of direct relevance to drug discovery.