Chemical staples and chemical probes to dissect dynamins cellular roles. Modulation of protein structure drives cellular function. Dynamin GTPase forms at least two macromolecular structures with different cellular functions. The drivers behind these different structures is unknown. In this project we will leverage our discoveries, and planned enhancements, of chemical biology probes that will modulate dynamin activity by inhibiting at three distinct sites, and one site that stimulates dynamin a ....Chemical staples and chemical probes to dissect dynamins cellular roles. Modulation of protein structure drives cellular function. Dynamin GTPase forms at least two macromolecular structures with different cellular functions. The drivers behind these different structures is unknown. In this project we will leverage our discoveries, and planned enhancements, of chemical biology probes that will modulate dynamin activity by inhibiting at three distinct sites, and one site that stimulates dynamin activity. It is known that Dynamin helices and rings are believed responsible for at least three in cell biological functions: in hormone, neutral and receptor internalisation; cellular mitosis and in actin dynamics. Prior to this work we have lacked the tools to understand the role of shape modulation of protein function.Read moreRead less
Venom-derived blood-brain-barrier shuttles. This project aims to discover new venom peptides capable of crossing the blood-brain barrier and to develop non-toxic peptide-based brain delivery systems. It addresses long-standing challenges and knowledge gaps in the delivery of macromolecules across biological barriers. Expected outcomes include an improved understanding of the strategies nature exploits to reach targets in the brain, mechanistic pathways to cross biological membranes, and innovati ....Venom-derived blood-brain-barrier shuttles. This project aims to discover new venom peptides capable of crossing the blood-brain barrier and to develop non-toxic peptide-based brain delivery systems. It addresses long-standing challenges and knowledge gaps in the delivery of macromolecules across biological barriers. Expected outcomes include an improved understanding of the strategies nature exploits to reach targets in the brain, mechanistic pathways to cross biological membranes, and innovative discovery and chemistry strategies to advance fundamental research across the chemical and biological sciences. Anticipated benefits include technological innovations relevant to Australia’s biotechnology sector and enhanced capacity for cross-disciplinary collaboration.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE240100134
Funder
Australian Research Council
Funding Amount
$796,206.00
Summary
Super-resolution platform to accelerate biological and molecular research. This application aims to establish a new molecular analysis platform integrating a microfluid capillary electrophoresis interface directly to a mass spectrometer with advanced data scanning technology. This enables label-free detection, quantitation and characterisation of intact proteins, lipids and metabolites with unprecedented sensitivity, resolution and throughput. It will enhance ARC projects spanning natural produc ....Super-resolution platform to accelerate biological and molecular research. This application aims to establish a new molecular analysis platform integrating a microfluid capillary electrophoresis interface directly to a mass spectrometer with advanced data scanning technology. This enables label-free detection, quantitation and characterisation of intact proteins, lipids and metabolites with unprecedented sensitivity, resolution and throughput. It will enhance ARC projects spanning natural product discovery, biotechnology, agriculture, and animal, plant and marine biology, as well as single-cell proteomics, lipidomics and metabolomics. It will ensure Australia remains at the forefront of molecular and biological research and create new training and collaborative opportunities both nationally and internationally.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE240100147
Funder
Australian Research Council
Funding Amount
$900,000.00
Summary
Revitalising NMR facilities in South Australia - Stage 2. The determination of molecular structure using Nuclear Magnetic Resonance (NMR) is a fundamental and powerful technique that is utilised by researchers across numerous disciplines. We are proposing to upgrade NMR facilities within South Australia in a carefully staged process so as to provide researchers access to state of the art experiments on modern instrumentation. In this proposal we aim to replace end of life components as well as p ....Revitalising NMR facilities in South Australia - Stage 2. The determination of molecular structure using Nuclear Magnetic Resonance (NMR) is a fundamental and powerful technique that is utilised by researchers across numerous disciplines. We are proposing to upgrade NMR facilities within South Australia in a carefully staged process so as to provide researchers access to state of the art experiments on modern instrumentation. In this proposal we aim to replace end of life components as well as provide increased sensitivity and capability by installing new probes. We aim to minimise duplication and maximise capability by undertaking a coordinated approach to NMR upgrades.Read moreRead less
Industrial Transformation Training Centres - Grant ID: IC230100046
Funder
Australian Research Council
Funding Amount
$5,000,000.00
Summary
ARC Training Centre for Radiochemical Technologies and Precision Radiopharmaceuticals. This project aims to train the next generation of radiochemists and discover new molecular approaches to harness radioactivity. Novel chemistry exploiting molecular incorporation of radioactive elements, stable chelation of metal radionuclides, bioconjugation methodologies, radioactivity capture via nanomaterials and cages, and the design of new peptidomimetic targeting molecules will deliver technological adv ....ARC Training Centre for Radiochemical Technologies and Precision Radiopharmaceuticals. This project aims to train the next generation of radiochemists and discover new molecular approaches to harness radioactivity. Novel chemistry exploiting molecular incorporation of radioactive elements, stable chelation of metal radionuclides, bioconjugation methodologies, radioactivity capture via nanomaterials and cages, and the design of new peptidomimetic targeting molecules will deliver technological advances to radiopharmaceutical science. Outcomes will include a highly-skilled workforce and enhanced commercial capacity to meet a rapidly escalating global radiopharmaceutical market. This project will provide significant benefits by securing an internal supply chain and know-how for cutting-edge radiochemical technologies.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101236
Funder
Australian Research Council
Funding Amount
$444,154.00
Summary
Chimeric molecules for precision protein modification. This project aims to address fundamental questions on how natural modifications of proteins cause functional changes inside cells. The project expects to generate new knowledge in the areas of organic chemistry and chemical biology through the development of a synthetic platform for the discovery of a novel class of chimeric molecules that can trigger precise modifications of proteins. Expected outcomes include a detailed understanding of ho ....Chimeric molecules for precision protein modification. This project aims to address fundamental questions on how natural modifications of proteins cause functional changes inside cells. The project expects to generate new knowledge in the areas of organic chemistry and chemical biology through the development of a synthetic platform for the discovery of a novel class of chimeric molecules that can trigger precise modifications of proteins. Expected outcomes include a detailed understanding of how specific modifications modulate protein and cellular function. Significant benefits of this interdisciplinary project include access to a new class of molecules for basic research that may also find use for cell engineering applications within the growing biotechnology sector in Australia.Read moreRead less
Advances in Peptide Synthesis: Exploiting Underutilised Functional Groups. The translation of therapeutically-relevant classes of peptides to the clinic is often limited by chemists' ability to synthesise these complex biomolecules efficiently and sustainably. This project aims to develop new tools for the preparation of designer peptides that are broadly inspired by an underutilised reactive group found in naturally-occurring peptide sequences. Expected outcomes encompass health and economic be ....Advances in Peptide Synthesis: Exploiting Underutilised Functional Groups. The translation of therapeutically-relevant classes of peptides to the clinic is often limited by chemists' ability to synthesise these complex biomolecules efficiently and sustainably. This project aims to develop new tools for the preparation of designer peptides that are broadly inspired by an underutilised reactive group found in naturally-occurring peptide sequences. Expected outcomes encompass health and economic benefits for the Australian community, including: the first approach to a class of promising antibiotic peptide natural product analogues, the development of a mild electrochemical approach to peptide modification, and the production of a library of novel amino acids for incorporation into potential antibiotic leads.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
Investigations into the antibacterial mechanism of action of cannabidiol. Cannabidiol (CBD) comes from a set of naturally occurring compounds, with a range of applications in mainstream culture. We have recently reported that CBD has excellent antimicrobial properties, with the ability to kill bacteria. This project aims to understand how CBD works by examining CBD-bacterial interactions at a genetic and molecular level. By understanding how CBD acts on and within bacterial cells, we can create ....Investigations into the antibacterial mechanism of action of cannabidiol. Cannabidiol (CBD) comes from a set of naturally occurring compounds, with a range of applications in mainstream culture. We have recently reported that CBD has excellent antimicrobial properties, with the ability to kill bacteria. This project aims to understand how CBD works by examining CBD-bacterial interactions at a genetic and molecular level. By understanding how CBD acts on and within bacterial cells, we can create fundamental new knowledge that could lead to the design of improved analogs of CBD to that can treat bacterial infections. As a much-needed completely new antibiotic class, this will lead to significant benefits, supporting Australia's National Strategy to combat the challenges posed by antimicrobial resistance.Read moreRead less