Thompson, Sam - University of Southampton

个人简介

Sam Thompson grew up in Lincolnshire and received his MChem from Exeter College, Oxford (2004) spending the final year with Prof. Ben Davis FRS in the historic Dyson Perrins Laboratory. He moved to St Edmund’s College, Cambridge for a PhD (2008) with Dr Martin Smith working on: (i) cascade routes to polycyclic alkaloids; and (ii) enantioselective carbon-carbon bond formation under phase-transfer catalysis. Returning to Oxford in 2009 he did a short medicinal chemistry postdoc sponsored by CRUK with Profs. Steve Davies and Angela Russell aimed at developing small molecule drugs for cancer targets. Between 2010 and 2016 he held Junior Research Fellowships at Pembroke College and Lady Margaret Hall, and was the team leader for the group of Prof. Andrew Hamilton FRS during his tenure as Vice-Chancellor at Oxford. This work was multidisciplinary – bringing together organic synthesis, supramolecular chemistry, and chemical biology to develop new approaches to mediate therapeutically relevant protein-protein interactions. Sam is also a passionate teacher having held Lectureships at several Oxford colleges, with particularly strong links to Christ Church, Lady Margaret Hall, and Pembroke.

研究领域

The inspiration and motivation for research in the group derives from the exquisite control that Nature exerts over structure and function – at both atomic and macromolecular levels. Unmet challenges in biology and medicine stem from gaps in our understanding of the basic science underlying these processes and a shortage of tools for the interrogation and manipulation of specific interactions. Proteins constitute a bio-macromolecular class of particular interest due to their essential roles in all life forms, performing myriad structural, catalytic, and signalling functions. They are critically important in numerous disease states including cancer, diabetes, and neurodegeneration. In this context our major long-term goals are to develop a deeper understanding of the structure/function relationships governing therapeutically relevant protein-protein interactions (PPIs) and protein-misfolding conditions, and to develop molecular tools for their manipulation. In our group organic synthesis and methodology are central tools allied with rigorous structural and conformational assignment by solution- and solid-phase methods (especially NMR and X-ray). Combined with techniques from the fields of supramolecular chemistry, physical organic, and chemical biology this makes for multi-disciplinary projects. We have established collaborations with experts in molecular- and cellular-biology, providing insights into the behaviour of our chemical probes in physiologically relevant settings. Recent work in our lab has focussed on the rational design of non-peptidic conformationally preorganised scaffolds that mimic key recognition elements of protein surfaces. These peptidomimetics have shown efficacy in mediating therapeutically relevant PPIs and intrinsically disordered proteins, including cancer and type II diabetes. Current work is focused on expanding this molecular toolkit for the recognition, interrogation, and regulation of disparate protein targets, including those implicated in ageing and neurodegeneration such as Alzheimer’s, Parkinson’s, and prion conditions.

近期论文

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Non-covalent S...O interactions control conformation in a scaffold that disrupts islet amyloid polypeptide fibrillation - Peacock, Hayden, Luo, Jinghui, Yamashita, Tohru, Luccarelli, James, Thompson, Sam and Hamilton, Andrew D. Published:2016Publication:Chemical ScienceVolume:7, (10)Page Range:6435-6439doi:10.1039/c6sc00756b B-strand mimetic foldamers rigidified through dipolar repulsion - German, Elizabeth A., Ross, Jonathan E., Knipe, Peter C., Don, Michaela F., Thompson, Sam and Hamilton, Andrew D. Published:2015Publication:Angewandte Chemie International EditionVolume:54, (9)Page Range:2649-2652doi:10.1002/anie.201410290 Diphenylacetylene-linked peptide strands induce bidirectional B-sheet formation - Lingard, Hannah, Han, Jeongmin T., Thompson, Amber L., Leung, Ivanhoe K.H., Scott, Richard T.W., Thompson, Sam and Hamilton, Andrew D. Published:2014Publication:Angewandte Chemie International EditionVolume:53, (14)Page Range:3650-3653doi:10.1002/anie.201309353 Aryl-linked imidazolidin-2-ones as non-peptidic beta-strand mimetics - Sutherell, Charlotte L., Thompson, Sam, Scott, Richard T.W. and Hamilton, Andrew D. Published:2012Publication:Chemical CommunicationsVolume:48, (79)Page Range:9834-9836doi:10.1039/C2CC34791A