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Lymphotropic prodrugs: a novel mechanism for targeted drug delivery. This project aims to design chemically modified drugs that target drug delivery specifically to white blood cells. This approach promises to maximise drug action and simultaneously reduce toxicity for diseases where lymphocytes are the major drug target. These include autoimmune disease, leukaemia, lymphoma, HIV, transplant rejection and diabetes.
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
Understanding endogenous allosteric modulators of G protein-coupled receptors. Major life science challenges include how chemicals outside cells signal to proteins inside, how this results in physiological responses, and how dysfunction of these processes leads to pathophysiology. Despite the critical importance of G protein-coupled receptors (GPCRs), much remains to be learned about their regulation by endogenous and synthetic molecules. This project aims to address this gap, by building on rec ....Understanding endogenous allosteric modulators of G protein-coupled receptors. Major life science challenges include how chemicals outside cells signal to proteins inside, how this results in physiological responses, and how dysfunction of these processes leads to pathophysiology. Despite the critical importance of G protein-coupled receptors (GPCRs), much remains to be learned about their regulation by endogenous and synthetic molecules. This project aims to address this gap, by building on recent ground-breaking studies that have been performed, by focusing on alternative binding sites of GPCRs called allosteric sites. The major hypothesis is that these allosteric sites are widespread across GPCRs because the body produces endogenous allosteric ligands that remain largely unidentified, but which can play vital roles in biology.Read moreRead less
Defining the biosynthesis and immunological properties of complex bacterial glycolipids. We will study how sugar-lipids are made by industrially, agriculturally and medically important bacteria, and how they interact with the immune system. This will provide new insights into cell wall biosynthesis of importance to the biotechnology industry and identify new reagents for manipulating the immune system.
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