Christopher Joseph Schofield (also known as Chris Schofield) is a Professor of Chemistry at the University of Oxford[1] and a Fellow of the Royal Society. Chris Schofield is a professor of organic chemistry at the University of Oxford, Department of Chemistry[2] and a Fellow of Hertford College.[3] Schofield studied functional, structural and mechanistic understanding of enzymes that employ oxygen and 2-oxoglutarate as a co-substrate.[4] His work has opened up new possibilities in antibiotic research,[5] oxygen sensing,[6] and gene regulation.[7]
After work on plant and microbial oxygenases,[4] he studied uncharacterised human oxygenases.[8] His research has identified unanticipated roles for oxygenases[9] in regulating gene expression, importantly in the cellular hypoxic response,[10] and has revealed new post-translational modifications to chromatin and RNA splicing proteins.[11] The work has identified new opportunities for medicinal intervention.[12]
Chris Schofield attended St Anselm's College catholic grammar school in Merseyside, then studied for a Bachelor of Science in chemistry at the University of Manchester and graduated with a first class honour (1979–1982). In 1982, he moved to Oxford to study for a DPhil with Professor Jack E. Baldwin. In 1985, he became a Departmental Demonstrator in the Dyson Perrins Laboratory, Oxford University followed by his appointment as a Lecturer in Chemistry[2] and a Fellow of Hertford College[3] in 1990. In 1998, he became professor of Chemistry,[1] and in 2011 he was appointed the Head of Organic Chemistry[13] at the Department of Chemistry, University of Oxford. In 2013, he was elected a Fellow of the Royal Society, FRS.[14]
The work in laboratory of Chris Schofield focuses on different areas of research, including:
Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric α,β-transcriptional complex[15] that mediates the cellular response to oxygen availability in multi-cellular organisms,[6][16] ranging from the simplest known animal Trichoplax adhaerens to humans.[4][6][17][18][19] Investigating the structures and mechanisms of the HIF prolyl hydroxylases is a current focus of the work.[10][20] The group solved crystal structures of PHD2[9][21] - one of the human prolyl hydroxylases - and discovered that the HIF asparaginyl hydroxylase also catalyses hydroxylation of conserved motifs,[22] the ankyrin repeat domain.
A current focus of the group is modification of histones, in particular oxygenase catalysed N-demethylation of histone methylated-lysine residues[7][23] – in collaboration with the Structural Genomics Consortium. The histone demethylases[24][25] are of interest both with respect to their links to diseases, including cancer[26][27] and inflammatory diseases,[28] as well as the role of methylation in transcriptional regulation.[29] Recent areas of interest include the fat mass and obesity protein[30][31] which was shown to be a nucleic acid demethylase[32] and JMJD6[33][34] which is a lysyl hydroxylase modifying RNA splicing protein.[11]
The 2-oxoglutarate (2OG)-dependent oxygenases are a superfamily of non-haem iron dependent oxygenases,[35] most of which use the Krebs cycle intermediate, 2OG, as a co-substrate.[36] The group are interested in understanding these enzymes[37] for their ability to catalyse synthetically difficult or 'impossible' reactions (e.g. the stereoselective hydroxylation of unactivated carbon-hydrogen bonds), for their diverse physiological roles,[8] and for their links to disease.[38] The research focuses on members of the family that are linked to disease, or can be targeted for the treatment of disease.[39][40] Techniques involved in this interdisciplinary research include proteomics,[41] X-ray crystallography,[42] nuclear magnetic resonance (NMR) spectroscopy,[43][44][45][46][47] biological mass spectrometry,[48] molecular biology,[49] enzyme kinetics,[50][51] protein-directed dynamic combinatorial chemistry[52][53] and organic synthesis/medicinal chemistry.[54][55]
Most clinically used antibiotics are based upon natural products.[5] The most important family of antibiotics contains a β-lactam ring, and includes the penicillin,[56] cephalosporin, clavam,[57] and carbapenem[58] antibiotics. The group's biosynthetic work has focused on the clavams[59] and carbapenems,[58] with a particular focus being on the mechanism and structures of enzymes that catalyse chemically 'interesting' steps.[60][61] The biggest threat to the continued use of β-lactam antibiotics is that of bacterial resistance. Schofield is currently working on the design and synthesis of enzyme inhibitors[62][63][64][65] for the metallo β-lactamases[66] – there are no clinically used inhibitor[67] of these enzymes but they pose a significant threat as they catalyse the hydrolysis of almost all clinically used β-lactam antibiotics.[68] A particular interest involves human metallo β-lactamases which share the same fold.[69]
2015-2020: Wellcome Trust Advanced Investigator Award (with Sir Peter Ratcliffe)
2013: Fellow of the Royal Society (London);[14] Member of EMBO; Fellow of the Royal Society of Biology, UK; Member of the Biochemical Society; Member of the Society for Experimental Biology, UK
2012: Finalist – Biotechnology and Biological Sciences Research Council 'Innovator of the Year'[70]
2011: Royal Society of Chemistry, Jeremy Knowles Award, UK;[71] Highly cited paper awards (e.g. Biochemical Journal, Bioorganic & Medicinal Chemistry Letters)
2009 – 2014: PI of ERC Advanced Investigator Grant SPA GA 2008 233240 (with Sir Peter Ratcliffe); Molecular Mechanism of Oxygen Sensing by Enzymes (MOOSE)
2000: Fellow of the Royal Society of Chemistry (London)