Developing a paradigm shift in new pharmaceutical and agrochemical design. This project will provide a paradigm shift in the design of new medicines and farming chemicals. The outcome of this research will be the efficient generation of diverse chemicals having real possibilities to improve global health and food security in the future.
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
The chemistry and biology of circular proteins. This project aims to develop plant-derived ultra-stable cyclic peptides for pharmaceutical and agricultural applications. The project will use innovative new methodologies for discovery, chemical synthesis and engineering of these molecules. It is expected that the project will contribute to high value biotechnology and agricultural industries in Australia. The proposed outcomes will include fundamental new knowledge on the biosynthesis of circular ....The chemistry and biology of circular proteins. This project aims to develop plant-derived ultra-stable cyclic peptides for pharmaceutical and agricultural applications. The project will use innovative new methodologies for discovery, chemical synthesis and engineering of these molecules. It is expected that the project will contribute to high value biotechnology and agricultural industries in Australia. The proposed outcomes will include fundamental new knowledge on the biosynthesis of circular proteins in plants, new approaches for their discovery and technologies for applying them as drug leads and agricultural products.Read moreRead less
Voltage-dependent structural changes in voltage-gated sodium channels. This project aims to provide insights into the structural rearrangements experienced by Nav channels, which are key components of animal nervous systems. Voltage-gated sodium (Nav) channels initiate action potentials in excitable cells. They open in response to membrane depolarisation then rapidly inactivate. Eukaryotic Nav channels contain four unique voltage-sensor domains (VSDs) that control how the channel responds to mem ....Voltage-dependent structural changes in voltage-gated sodium channels. This project aims to provide insights into the structural rearrangements experienced by Nav channels, which are key components of animal nervous systems. Voltage-gated sodium (Nav) channels initiate action potentials in excitable cells. They open in response to membrane depolarisation then rapidly inactivate. Eukaryotic Nav channels contain four unique voltage-sensor domains (VSDs) that control how the channel responds to membrane potential changes. Recently reported crystal structures of bacterial Nav channels have greatly advanced the field, but these channels contain four identical VSDs and have different inactivation properties. Thus, much remains to be learnt about the conformational plasticity of eukaryotic Nav channel VSDs. The project plans to use animal toxins to capture eukaryotic VSDs in defined states of the gating cycle for detailed structural analysis using nuclear magnetic resonance and X-ray crystallography.Read moreRead less
Synthesis and Biological Evaluation of Australian Sponge Metabolites. The development of concise and flexible syntheses of Australian marine natural products and analogues of ecological/therapeutic significance will emerge. Such activities will lead to the identification and evaluation of molecular entities of value in managing marine environments and help to enhance chemical synthesis capacity in Australia.