Research Christopher J. Schofield

1 research

1.1 molecular mechanisms of hypoxic response
1.2 chemical basis of epigenetics
1.3 structural , functional studies on 2og oxygenases
1.4 antibiotics: biosynthesis , resistance mechanisms

research

the work in laboratory of chris schofield focuses on different areas of research, including:

molecular mechanisms of hypoxic response

hypoxia-inducible factor-1 (hif-1) heterodimeric α,β-transcriptional complex mediates cellular response oxygen availability in multi-cellular organisms, ranging simplest known animal trichoplax adhaerens humans. investigating structures , mechanisms of hif prolyl hydroxylases current focus of work. group solved crystal structures of phd2 - 1 of human prolyl hydroxylases - , discovered hif asparaginyl hydroxylase catalyses hydroxylation of conserved motifs, ankyrin repeat domain.

chemical basis of epigenetics

a current focus of group modification of histones, in particular oxygenase catalysed n-demethylation of histone methylated-lysine residues – in collaboration structural genomics consortium. histone demethylases of interest both respect links diseases, including cancer , inflammatory diseases, role of methylation in transcriptional regulation. recent areas of interest include fat mass , obesity protein shown nucleic acid demethylase , jmjd6 lysyl hydroxylase modifying rna splicing protein.

structural , functional studies on 2og oxygenases

the 2-oxoglutarate (2og)-dependent oxygenases superfamily of non-haem iron dependent oxygenases, of use krebs cycle intermediate, 2og, co-substrate. group interested in understanding these enzymes ability catalyse synthetically difficult or impossible reactions (e.g. stereoselective hydroxylation of unactivated carbon-hydrogen bonds), diverse physiological roles, , links disease. research focuses on members of family linked disease, or can targeted treatment of disease. techniques involved in interdisciplinary research include proteomics, x-ray crystallography, nuclear magnetic resonance (nmr) spectroscopy, biological mass spectrometry, molecular biology, enzyme kinetics, , organic synthesis/medicinal chemistry.

antibiotics: biosynthesis , resistance mechanisms

most clinically used antibiotics based upon natural products. important family of antibiotics contains β-lactam ring, , includes penicillin, cephalosporin, clavam, , carbapenem antibiotics. group s biosynthetic work has focused on clavams , carbapenems, particular focus being on mechanism , structures of enzymes catalyse chemically interesting steps. biggest threat continued use of β-lactam antibiotics of bacterial resistance. prof schofield working on design , synthesis of enzyme inhibitors metallo β-lactamases – there no clinically used inhibitor of these enzymes pose significant threat catalyse hydrolysis of clinically used β-lactam antibiotics. particular interest involves human metallo β-lactamases share same fold.