Development of small molecule primary sulfonamides as new drugs for malaria. Malaria is a major global health threat, causing approximately 800,000 deaths annually. Lives can be saved if patients are treated. The use of current antimalarial drugs is limited by drug resistance, low activity and poor safety. This project investigates the effectiveness of a new class of molecule as a safe drug treatment option to kill malaria parasites.
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
Development of effective peptide-based drugs. There is huge interest in the development of bioactive peptides and proteins for the treatment of a wide range of diseases. The aim of this research project is to develop potent and effective peptide-based drugs that are able to resist the body's natural degradation pathways so that they can reach their biological target and act as effective drugs.
Towards the sustainable discovery and development of new antibiotics. This project aims to define how to access silent biosynthetic genes within microbial genome to facilitate access to new chemical diversity hidden within microbial genomes. Using interdisciplinary approaches in genome mining and metabolomics technologies, the project expects to inspire and enable the future design of more effective antibiotics. Expected outcomes from this program include define new microbial defence molecules, ....Towards the sustainable discovery and development of new antibiotics. This project aims to define how to access silent biosynthetic genes within microbial genome to facilitate access to new chemical diversity hidden within microbial genomes. Using interdisciplinary approaches in genome mining and metabolomics technologies, the project expects to inspire and enable the future design of more effective antibiotics. Expected outcomes from this program include define new microbial defence molecules, to meet future demands in agrochemical and environmental sciences. It will also train future scientists and develop international collaborations. This should provide significant benefit, including a higher-quality workforce for research and innovation, positioning Australia at the forefront of drug discovery. Read moreRead less
Time to shine for constrained peptides as next-generation pharmaceuticals. Current methods for the screening and generation of peptide and protein drugs are laborious, expensive and often incompatible with the biological systems used in pharmaceutical industries. Leveraging recent advancements in chemistry and molecular biology, this project aims to improve the design, synthesis and screening of peptide-based pharmaceuticals. Key research outcomes are innovative biocompatible chemical transforma ....Time to shine for constrained peptides as next-generation pharmaceuticals. Current methods for the screening and generation of peptide and protein drugs are laborious, expensive and often incompatible with the biological systems used in pharmaceutical industries. Leveraging recent advancements in chemistry and molecular biology, this project aims to improve the design, synthesis and screening of peptide-based pharmaceuticals. Key research outcomes are innovative biocompatible chemical transformations for the screening of large peptide libraries, to unleash the revolutionary potential of constrained peptides in drug development. Expected benefits are reliable and cost-effective technologies for the rapid production of biologically active molecules for future targeted use in human and agricultural pharmaceuticals.Read moreRead less
The potential of membranes – peptide engineering to modulate ion channels. This project aims to develop a platform technology to identify new and selective sodium channel inhibitors based on ultra-stable venom peptides that can interact with and cross membranes. Sodium channels are involved in almost all aspects of human physiology. The ability to selectively inhibit individual sodium channel subtypes and to understand what drives peptides' ability to cross membranes would be a major achievement ....The potential of membranes – peptide engineering to modulate ion channels. This project aims to develop a platform technology to identify new and selective sodium channel inhibitors based on ultra-stable venom peptides that can interact with and cross membranes. Sodium channels are involved in almost all aspects of human physiology. The ability to selectively inhibit individual sodium channel subtypes and to understand what drives peptides' ability to cross membranes would be a major achievement and lead to new neuroscience research tools and technologies. This project’s proposed technology could be translated into new knowledge relevant to the biotechnology industry.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
New platform technologies for the chemical synthesis of post-translationally modified proteins. The last decade has seen an explosion in the number of protein drugs approved for use in the clinic, a large proportion of which possess post-translational modifications (PTMs). These modified protein drugs are produced and sold as mixtures which has led to difficulties in understanding the role of specific PTMs on activity and in gaining clinical approval for candidate drugs. This project will provid ....New platform technologies for the chemical synthesis of post-translationally modified proteins. The last decade has seen an explosion in the number of protein drugs approved for use in the clinic, a large proportion of which possess post-translational modifications (PTMs). These modified protein drugs are produced and sold as mixtures which has led to difficulties in understanding the role of specific PTMs on activity and in gaining clinical approval for candidate drugs. This project will provide a fundamental solution to this problem through the development of novel synthetic methods and a powerful new platform technology for accessing PTM proteins in pure form. The utility of this technology will be demonstrated through its use in the total chemical synthesis of a range of PTM proteins for applications in biology and medicine.Read moreRead less
Metals in biocatalysis. Metals and enzymes are essential for the chemistry of life. This project will aim to garner the potential of metal-dependent enzymes to develop new drugs against osteoporosis, combat the spread of antibiotics resistance and optimise some of these enzymes to detoxify pesticide-polluted environments, thus contributing to global health and food security.