Control of immune recognition and response by microbial metabolites. This project aims to study immune recognition of microbial metabolites and develop reagents to control immune responses. Chemical synthesis will be used to develop new antigens for unconventional T cells and the first soluble agonists and antagonists of a glycolipid-sensing immune receptor. Expected outcomes include the discovery of new immune effectors, broadening our knowledge of the repertoire of small molecules that can be ....Control of immune recognition and response by microbial metabolites. This project aims to study immune recognition of microbial metabolites and develop reagents to control immune responses. Chemical synthesis will be used to develop new antigens for unconventional T cells and the first soluble agonists and antagonists of a glycolipid-sensing immune receptor. Expected outcomes include the discovery of new immune effectors, broadening our knowledge of the repertoire of small molecules that can be sensed by the immune system, and developing chemical approaches to promote or dampen immune responses. Major benefits include research training in chemical biology, strengthened international linkages and fundamental insights into the chemical basis of immune recognition and response.Read moreRead less
Chemical-biology approaches to pathway selective adenosine receptor ligands. This project aims to develop new chemical-biology tools and approaches for selectively targeting signalling pathways mediated by G protein-coupled receptors (GPCR). GPCRs are an important family of cell surface signalling proteins that are responsible for the regulation of numerous vital physiological functions. The A1 adenosine receptor is an important model and therapeutically relevant GPCR that will be the focus of t ....Chemical-biology approaches to pathway selective adenosine receptor ligands. This project aims to develop new chemical-biology tools and approaches for selectively targeting signalling pathways mediated by G protein-coupled receptors (GPCR). GPCRs are an important family of cell surface signalling proteins that are responsible for the regulation of numerous vital physiological functions. The A1 adenosine receptor is an important model and therapeutically relevant GPCR that will be the focus of this project. Compounds known as bitopic ligands, which can interact with distinct binding sites (termed orthosteric and allosteric sites), will be explored as pathway selective agents capable of activating the signalling pathways mediating the desired effect in preference to those producing adverse effects. Longer-term benefits include the identification of bioactive compounds with more selective modes of action and improved safety profiles.Read moreRead less
How lipid binding proteins shape the activity of nuclear hormone receptors. This project aims to explore how a family of lipid binding proteins control organ specific activation of nuclear receptors – receptors that play a key role in generating energy and are critical for life. The project will employ chemical, molecular, cell biology approaches to generate new knowledge about lipid binding protein-receptor interactions and how these complexes dictate receptor activation. The outcomes could pro ....How lipid binding proteins shape the activity of nuclear hormone receptors. This project aims to explore how a family of lipid binding proteins control organ specific activation of nuclear receptors – receptors that play a key role in generating energy and are critical for life. The project will employ chemical, molecular, cell biology approaches to generate new knowledge about lipid binding protein-receptor interactions and how these complexes dictate receptor activation. The outcomes could provide a roadmap to design drugs that interact with the right protein in the right tissue and in doing so dramatically enhance drug specificity. This will benefit the success of drug treatments which require stimulation of a therapeutic response at a target site, and avoidance of potentially toxic activity at other locations.Read moreRead less
Dissecting a major sulfur cycling pathway: sulfoglycolysis. This project will elucidate the molecular details of sulfoglycolysis, a group of metabolic pathways through which the sulfur-containing sugar sulfoquinovose is catabolized. The project will employ an integrated metabolomic, chemical, biochemical and structural approach to dissect how various sulfoglycolytic organisms degrade sulfoquinovose. This project will deliver a deeper understanding of this major biochemical pathway and develop ne ....Dissecting a major sulfur cycling pathway: sulfoglycolysis. This project will elucidate the molecular details of sulfoglycolysis, a group of metabolic pathways through which the sulfur-containing sugar sulfoquinovose is catabolized. The project will employ an integrated metabolomic, chemical, biochemical and structural approach to dissect how various sulfoglycolytic organisms degrade sulfoquinovose. This project will deliver a deeper understanding of this major biochemical pathway and develop new chemical and metabolic approaches to manipulate sulfur cycling in the environment. Benefits will include biotechnology applications of newly discovered proteins, and sustainable approaches to reduce our dependence on agricultural fertilisers.Read moreRead less
Antimicrobial and anti-Leishmanial bismuth compounds and materials. The project aims to develop the bioinorganic and medicinal chemistry of bismuth and related metals to address two global health issues: parasitic infections (principally Leishmaniasis) and antibacterial resistance. Through targeting serious microbial infections, the project will research the chemical, physical, structural and biological properties of bismuth and related metals. The project will form bio-protective materials and ....Antimicrobial and anti-Leishmanial bismuth compounds and materials. The project aims to develop the bioinorganic and medicinal chemistry of bismuth and related metals to address two global health issues: parasitic infections (principally Leishmaniasis) and antibacterial resistance. Through targeting serious microbial infections, the project will research the chemical, physical, structural and biological properties of bismuth and related metals. The project will form bio-protective materials and surfaces through incorporating bismuth and its compounds into polymer matrices. It will establish the complexes’ chemical biology and toxicology through scrutinising cellular mechanisms, particularly modern metallomic techniques. New compounds developed may address the urgent and significant health issue of antibiotic resistance and help address poorly treated parasitic infections.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
A new platform technology for gene therapy . The project aims to make a landmark contribution to biological science by enabling programmed delivery of therapeutic payloads from biocompatible materials. It will employ a novel synthetic biology approach to form two distinct peptide-enabled molecular architectures in a single system. This is expected to deliver a platform technology that will allow successful programmed delivery of viral vectors. The project is likely to deliver significant societa ....A new platform technology for gene therapy . The project aims to make a landmark contribution to biological science by enabling programmed delivery of therapeutic payloads from biocompatible materials. It will employ a novel synthetic biology approach to form two distinct peptide-enabled molecular architectures in a single system. This is expected to deliver a platform technology that will allow successful programmed delivery of viral vectors. The project is likely to deliver significant societal benefit as a fundamental scientific platform, improving Australia's capacity and impact in the agriculture and the healthcare sectors. The platform technology has the potential to increase the quality of life for patients and their carers, while also produce fitter, healthier livestock.Read moreRead less
Developing new tools for chemical biology. We will develop new synthetic strategies to support the development of small molecule chemical probes that bind with high affinity and specificity to a target protein. Such chemical probes are invaluable in elucidating the role of specific proteins in biological pathways. Our novel strategy aims to be rapid, efficient in its use of materials and widely applicable to a range of different protein targets. The core of our approach involves using biophysica ....Developing new tools for chemical biology. We will develop new synthetic strategies to support the development of small molecule chemical probes that bind with high affinity and specificity to a target protein. Such chemical probes are invaluable in elucidating the role of specific proteins in biological pathways. Our novel strategy aims to be rapid, efficient in its use of materials and widely applicable to a range of different protein targets. The core of our approach involves using biophysical binding assays to characterise compounds that are produced on small scale using parallel chemistry. This approach will enable better chemical probes to be developed more rapidly at lower cost than is currently possible.Read moreRead less