Exploring metabotropic glutamate receptor 5 bias, allostery and heteromers. This project aims to provide novel mechanistic and structural insights into metabotropic glutamate receptor 5 (mGlu5) function. The mGlu5 is an essential regulator of neurotransmission and higher order brain functions including learning and memory. This project expects to expand knowledge of the fundamental biological processes engaged by mGlu5 through exploration of three novel paradigms of receptor activity: allostery, ....Exploring metabotropic glutamate receptor 5 bias, allostery and heteromers. This project aims to provide novel mechanistic and structural insights into metabotropic glutamate receptor 5 (mGlu5) function. The mGlu5 is an essential regulator of neurotransmission and higher order brain functions including learning and memory. This project expects to expand knowledge of the fundamental biological processes engaged by mGlu5 through exploration of three novel paradigms of receptor activity: allostery, bias and heteromerisation. Expected outcomes also include generation of new pharmacological tools through interdisciplinary collaborative research between multiple institutions. There is significant expected economic benefit through commercialisation of new tools and facilitation of novel drug discovery.Read moreRead less
Breaking it down: Dissecting the mechanism and exploring new inhibition strategies for polysaccharide cleaving enzymes. Mannose, a common carbohydrate building block, is present in a wide variety of complex polysaccharides including energy storage polymers and glycans attached to proteins. The enzymes that degrade these mannose-rich polymers, termed mannosidases, are important in biofuel production and human health and disease. This project will study a range of mannosidases to chemically and st ....Breaking it down: Dissecting the mechanism and exploring new inhibition strategies for polysaccharide cleaving enzymes. Mannose, a common carbohydrate building block, is present in a wide variety of complex polysaccharides including energy storage polymers and glycans attached to proteins. The enzymes that degrade these mannose-rich polymers, termed mannosidases, are important in biofuel production and human health and disease. This project will study a range of mannosidases to chemically and structurally define their mechanisms and establish strategies to allow intervention in mannosidase-specific disease processes. This work will inform strategies to engineer new enzymes for future biotechnology and industrial applications including sustainable chemical manufacturing, and underpin the development of innovative drugs for treating fungal infections and cancer.Read moreRead less
The hidden secondary metabolite biosynthetic potential of fungi. This proposal aims to develop synthetic biology tools to allow rapid access to the hidden metabolites encoded in fungal genomes and discover how they interact with plant and animal hosts. Genome sequencing reveals that fungi harbour vast hidden potential for biosynthesis of bioactive small molecules. The lack of tools to efficiently access this hidden potential has hindered the ability to develop this uncharted chemical diversity f ....The hidden secondary metabolite biosynthetic potential of fungi. This proposal aims to develop synthetic biology tools to allow rapid access to the hidden metabolites encoded in fungal genomes and discover how they interact with plant and animal hosts. Genome sequencing reveals that fungi harbour vast hidden potential for biosynthesis of bioactive small molecules. The lack of tools to efficiently access this hidden potential has hindered the ability to develop this uncharted chemical diversity for pharmaceutics and agriculture, and understand their biological roles in pathogens. Expected outcomes include sources of bioactive molecules and better management of fungal diseases in crops and humans.Read moreRead less