Understanding allosteric modulation and functional selectivity at G Protein-Coupled Receptors (GPCRs). GPCRs are an important superfamily of proteins that are involved in a myriad of physiological processes and a wide range of serious illnesses. This project seeks to gain a more detailed understanding of new mechanisms of GPCR modulation and function that will be of direct relevance to drug discovery.
Dissecting catalysis and inhibition of a unique endo-acting mannose-processing glycosidase. Defects in the attachment of carbohydrates to proteins are a hallmark of diseases such as cancer and viral infection. This project will dissect the molecular details of the bond-making and breaking steps that occur during the synthesis of glycoproteins assisting in the development of innovative new drugs.
Biogenesis inspired total synthesis of natural products. The project will study the chemical synthesis of a number of novel natural products. Most significantly, this project will deliver new methods for organic synthesis of complex molecules. The rewards from the total synthesis of bioactive compounds are enormous for the community and in the education and training of scientists.
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
Using chemistry to illuminate sulfoglycolysis, a major organosulfur pathway. This project aims to develop a detailed molecular description of the sulfoglycolysis pathway, a major pathway involved in cycling an abundant sulfolipid. The project will use an integrated chemical, biochemical and structural approach to illuminate how sulfoglycolysis degrades sulfolipid to access its elemental and energy constituents. Expected outcomes include an advanced understanding of the biosulfur cycle, the devel ....Using chemistry to illuminate sulfoglycolysis, a major organosulfur pathway. This project aims to develop a detailed molecular description of the sulfoglycolysis pathway, a major pathway involved in cycling an abundant sulfolipid. The project will use an integrated chemical, biochemical and structural approach to illuminate how sulfoglycolysis degrades sulfolipid to access its elemental and energy constituents. Expected outcomes include an advanced understanding of the biosulfur cycle, the development of new chemical approaches to manipulate sulfur cycling for agricultural and biotechnology applications, and deepened ties to leading international researchers. Potential benefits include new strategies to reduce dependence on agricultural fertilisers, promote gut wellbeing, and control insect pests.Read moreRead less
Total Synthesis of Myxobacteria Metabolites and Analogues. This project will investigate the total chemical synthesis of complex myxobacteria metabolites. In addition, the synthesis of new analogues of some of these natural products will also be investigated. The project endeavours to develop new methods for chemical synthesis and also to produce new therapeutic products which may possess greater efficacy and superior biological activities than the natural compounds. Most significantly, this pro ....Total Synthesis of Myxobacteria Metabolites and Analogues. This project will investigate the total chemical synthesis of complex myxobacteria metabolites. In addition, the synthesis of new analogues of some of these natural products will also be investigated. The project endeavours to develop new methods for chemical synthesis and also to produce new therapeutic products which may possess greater efficacy and superior biological activities than the natural compounds. Most significantly, this project will deliver natural and new compounds for analysis of anti-cancer activity. The rewards of the development of new synthetic methods are enormous for the community and in the education of our scientists.Read moreRead less
Chemical probes for the study of a unique enzyme from Mycobacterium tuberculosis. The design and chemical synthesis of molecules that selectively inhibit pathogen-specific enzymes is a validated approach toward new therapeutic agents. Mycobacterium tuberculosis contains a unique cytochrome P450 enzyme that catalyses an unusual chemical transformation to generate the product mycocyclosin. This research project will synthesise chemical probes to study the mechanism of this enzyme and the biologica ....Chemical probes for the study of a unique enzyme from Mycobacterium tuberculosis. The design and chemical synthesis of molecules that selectively inhibit pathogen-specific enzymes is a validated approach toward new therapeutic agents. Mycobacterium tuberculosis contains a unique cytochrome P450 enzyme that catalyses an unusual chemical transformation to generate the product mycocyclosin. This research project will synthesise chemical probes to study the mechanism of this enzyme and the biological role of mycocyclosin. Selective inhibitors of the enzyme will be developed, which will provide a foundation for the exploitation of these molecules in cellular research and medicine.Read moreRead less
Allosteric and Bitopic Ligands Acting at G Protein-Coupled Receptors. This project seeks to gain a more detailed understanding of the mechanisms of the function of G protein-coupled receptors (GPCRs) using novel chemical tools. GPCRs are the largest group of cell surface signalling proteins and are responsible for the regulation of numerous vital physiological functions. They are the target of over 30 per cent of currently used pharmaceuticals. Despite their importance, much remains to be learne ....Allosteric and Bitopic Ligands Acting at G Protein-Coupled Receptors. This project seeks to gain a more detailed understanding of the mechanisms of the function of G protein-coupled receptors (GPCRs) using novel chemical tools. GPCRs are the largest group of cell surface signalling proteins and are responsible for the regulation of numerous vital physiological functions. They are the target of over 30 per cent of currently used pharmaceuticals. Despite their importance, much remains to be learned about the regulation of GPCRs by small molecules. This project aims to address this gap by focusing on novel regions on these proteins, termed allosteric sites, to explore novel modes of GPCR regulation which may offer the potential of identifying pathway selective agents.Read moreRead less
Supercharging antioxidant capacity. This project aims to deliver improved, tailor-made antioxidants that can better protect key biomolecules and other materials against collateral damage from oxidants within cells. Through fundamental chemistry research, this project aims to understand the relationship between antioxidant capacity and molecular structure, and, through computational chemistry, develop a predictive tool. This, in turn, will provide the means to design molecules that better protect ....Supercharging antioxidant capacity. This project aims to deliver improved, tailor-made antioxidants that can better protect key biomolecules and other materials against collateral damage from oxidants within cells. Through fundamental chemistry research, this project aims to understand the relationship between antioxidant capacity and molecular structure, and, through computational chemistry, develop a predictive tool. This, in turn, will provide the means to design molecules that better protect against oxidative processes. The expected outcome is improved technology to heal tissue damage and inflammation caused by enzymes.Read moreRead less
Unravelling the immunology of complex glycolipids by chemical synthesis. This project seeks to develop new approaches to chemically synthesise bacterial and fungal glycolipids and develop a molecular-level understanding of their effect on the immune system. Bacterial and fungal glycolipids are exotic chemical species that act as danger signals to prime and modulate our innate immune responses. These complex glycolipids possess powerful immunological activities that continue to shape our understa ....Unravelling the immunology of complex glycolipids by chemical synthesis. This project seeks to develop new approaches to chemically synthesise bacterial and fungal glycolipids and develop a molecular-level understanding of their effect on the immune system. Bacterial and fungal glycolipids are exotic chemical species that act as danger signals to prime and modulate our innate immune responses. These complex glycolipids possess powerful immunological activities that continue to shape our understanding of innate immunity, yet cannot be acquired from natural sources in the quantities and purity needed. The approaches expected to be developed in the project will be used to illuminate molecular details of immune signalling through pattern recognition receptors and presentation on specialised glycolipid antigen-presenting molecules. Outcomes may include new ways to fight disease and promote health by marshalling the resources of the immune system.Read moreRead less