Christopher J. Schofield
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Christopher Joseph Schofield (also known as Chris Schofield) is the Head of Organic Chemistry at the
University of Oxford , mottoeng = The Lord is my light , established = , endowment = £6.1 billion (including colleges) (2019) , budget = £2.145 billion (2019–20) , chancellor ...
and a
Fellow of the Royal Society Fellowship of the Royal Society (FRS, ForMemRS and HonFRS) is an award granted by the judges of the Royal Society of London to individuals who have made a "substantial contribution to the improvement of natural knowledge, including mathemat ...
. Chris Schofield is a professor of
organic chemistry Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, ...
at the University of Oxford, Department of Chemistry and a Fellow of
Hertford College Hertford College ( ), previously known as Magdalen Hall, is a constituent college of the University of Oxford in England. It is located on Catte Street in the centre of Oxford, directly opposite the main gate to the Bodleian Library. The colle ...
. Prof Schofield studied functional, structural and mechanistic understanding of
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s that employ oxygen and 2-oxoglutarate as a co-substrate. His work has opened up new possibilities in antibiotic research, oxygen sensing, and
gene regulation Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are wi ...
. After work on plant and microbial
oxygenase An oxygenase is any enzyme that oxidizes a substrate by transferring the oxygen from molecular oxygen O2 (as in air) to it. The oxygenases form a class of oxidoreductases; their EC number is EC 1.13 or EC 1.14. Discoverers Oxygenases were disco ...
s, he studied uncharacterised human oxygenases. His research has identified unanticipated roles for
oxygenase An oxygenase is any enzyme that oxidizes a substrate by transferring the oxygen from molecular oxygen O2 (as in air) to it. The oxygenases form a class of oxidoreductases; their EC number is EC 1.13 or EC 1.14. Discoverers Oxygenases were disco ...
s in regulating gene expression, importantly in the cellular
hypoxic Hypoxia means a lower than normal level of oxygen, and may refer to: Reduced or insufficient oxygen * Hypoxia (environmental), abnormally low oxygen content of the specific environment * Hypoxia (medical), abnormally low level of oxygen in the t ...
response, and has revealed new
post-translational modification Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribos ...
s to
chromatin Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...
and RNA splicing proteins. The work has identified new opportunities for medicinal intervention.


Education

Chris Schofield attended St Anselm's College catholic
grammar school A grammar school is one of several different types of school in the history of education in the United Kingdom and other English-speaking countries, originally a school teaching Latin, but more recently an academically oriented secondary school ...
in Merseyside, then studied for a Bachelor of Science in chemistry at the
University of Manchester , mottoeng = Knowledge, Wisdom, Humanity , established = 2004 – University of Manchester Predecessor institutions: 1956 – UMIST (as university college; university 1994) 1904 – Victoria University of Manchester 1880 – Victoria Univ ...
and graduated with a first class honour (1979–1982). In 1982, he moved to
Oxford Oxford () is a city in England. It is the county town and only city of Oxfordshire. In 2020, its population was estimated at 151,584. It is north-west of London, south-east of Birmingham and north-east of Bristol. The city is home to the ...
to study for a
DPhil A Doctor of Philosophy (PhD, Ph.D., or DPhil; Latin: or ') is the most common degree at the highest academic level awarded following a course of study. PhDs are awarded for programs across the whole breadth of academic fields. Because it is ...
with Professor Jack E. Baldwin. In 1985, he became a Departmental Demonstrator in the
Dyson Perrins Laboratory The Dyson Perrins Laboratory is in the science area of the University of Oxford and was the main centre for research into organic chemistry of the University from its foundation in 1916 until its closure as a research laboratory in 2003. Until 2 ...
,
Oxford University Oxford () is a city in England. It is the county town and only city of Oxfordshire. In 2020, its population was estimated at 151,584. It is north-west of London, south-east of Birmingham and north-east of Bristol. The city is home to th ...
followed by his appointment as a Lecturer in Chemistry and a
Fellow A fellow is a concept whose exact meaning depends on context. In learned or professional societies, it refers to a privileged member who is specially elected in recognition of their work and achievements. Within the context of higher education ...
of
Hertford College Hertford College ( ), previously known as Magdalen Hall, is a constituent college of the University of Oxford in England. It is located on Catte Street in the centre of Oxford, directly opposite the main gate to the Bodleian Library. The colle ...
in 1990. In 1998, he became professor of Chemistry, and in 2011 he was appointed the Head of Organic Chemistry at the Department of Chemistry, University of Oxford. In 2013, he was elected a
Fellow of the Royal Society Fellowship of the Royal Society (FRS, ForMemRS and HonFRS) is an award granted by the judges of the Royal Society of London to individuals who have made a "substantial contribution to the improvement of natural knowledge, including mathemat ...
, FRS.


Research

The work in laboratory of Chris Schofield focuses on different areas of research, including:


Molecular Mechanisms of the Hypoxic Response

Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric α,β-transcriptional complex that mediates the cellular response to oxygen availability in multi-cellular organisms, ranging from the simplest known animal ''
Trichoplax adhaerens ''Trichoplax adhaerens'' is one of the three named species in the phylum Placozoa. The others are '' Hoilungia hongkongensis'' and '' Polyplacotoma mediterranea''. The Placozoa is a basal group of multicellular animals (metazoa). ''Trichoplax'' ...
'' to humans. Investigating the structures and mechanisms of the HIF prolyl hydroxylases is a current focus of the work. The group solved crystal structures of PHD2 - one of the human
prolyl hydroxylase Procollagen-proline dioxygenase, commonly known as prolyl hydroxylase, is a member of the class of enzymes known as alpha-ketoglutarate-dependent hydroxylases. These enzymes catalyze the incorporation of oxygen into organic substrates through a mec ...
s - and discovered that the HIF asparaginyl hydroxylase also catalyses hydroxylation of conserved motifs, the
ankyrin repeat The ankyrin repeat is a 33-residue motif in proteins consisting of two alpha helices separated by loops, first discovered in signaling proteins in yeast Cdc10 and ''Drosophila'' Notch. Domains consisting of ankyrin tandem repeats mediate prot ...
domain.


Chemical Basis of Epigenetics

A current focus of the group is modification of histones, in particular oxygenase catalysed ''N''-demethylation of histone methylated- lysine residues – in collaboration with the Structural Genomics Consortium. The histone demethylases are of interest both with respect to their links to diseases, including cancer and
inflammatory diseases Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecu ...
, as well as the role of methylation in
transcriptional regulation In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from al ...
. Recent areas of interest include the fat mass and obesity protein which was shown to be a nucleic acid demethylase and
JMJD6 Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6 is an enzyme that in humans is encoded by the ''JMJD6'' gene. Function This gene encodes a nuclear protein with a JmjC domain. JmjC domain-containing proteins belong to the alpha-ke ...
which is a lysyl hydroxylase modifying RNA splicing protein.


Structural and Functional Studies on 2OG Oxygenases

The 2-oxoglutarate (2OG)-dependent oxygenases are a superfamily of non-haem iron dependent
oxygenase An oxygenase is any enzyme that oxidizes a substrate by transferring the oxygen from molecular oxygen O2 (as in air) to it. The oxygenases form a class of oxidoreductases; their EC number is EC 1.13 or EC 1.14. Discoverers Oxygenases were disco ...
s, most of which use the
Krebs cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and protein ...
intermediate, 2OG, as a
co-substrate A cofactor is a non-protein chemical compound or metallic ion that is required for an enzyme's role as a catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can be considered "helper molecules" that ass ...
. The group are interested in understanding these enzymes for their ability to catalyse synthetically difficult or 'impossible' reactions (''e.g.'' the
stereoselective In chemistry, stereoselectivity is the property of a chemical reaction in which a single reactant forms an unequal mixture of stereoisomers during a non-stereospecific creation of a new stereocenter or during a non-stereospecific transformation of ...
hydroxylation of unactivated carbon-hydrogen bonds), for their diverse physiological roles, and for their links to disease. The research focuses on members of the family that are linked to disease, or can be targeted for the treatment of disease. Techniques involved in this interdisciplinary research include proteomics,
X-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
,
nuclear magnetic resonance Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are perturbed by a weak oscillating magnetic field (in the near field) and respond by producing an electromagnetic signal with a ...
(NMR) spectroscopy, biological mass spectrometry,
molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
,
enzyme kinetics Enzyme kinetics is the study of the rates of enzyme-catalysed chemical reactions. In enzyme kinetics, the reaction rate is measured and the effects of varying the conditions of the reaction are investigated. Studying an enzyme's kinetics in thi ...
, protein-directed dynamic combinatorial chemistry and organic synthesis/
medicinal chemistry Medicinal or pharmaceutical chemistry is a scientific discipline at the intersection of chemistry and pharmacy involved with designing and developing pharmaceutical drugs. Medicinal chemistry involves the identification, synthesis and developme ...
.


Antibiotics: Biosynthesis and Resistance Mechanisms

Most clinically used
antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...
are based upon natural products. The most important family of antibiotics contains a
β-lactam A beta-lactam (β-lactam) ring is a four-membered lactam. A ''lactam'' is a cyclic amide, and ''beta''-lactams are named so because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl. The simplest β-lactam possible is ...
ring, and includes the penicillin, cephalosporin, clavam, and
carbapenem Carbapenems are a class of very effective antibiotic agents most commonly used for the treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. ...
antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...
. The group's biosynthetic work has focused on the clavams and
carbapenem Carbapenems are a class of very effective antibiotic agents most commonly used for the treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. ...
s, with a particular focus being on the mechanism and structures of enzymes that catalyse chemically 'interesting' steps. The biggest threat to the continued use of
β-lactam A beta-lactam (β-lactam) ring is a four-membered lactam. A ''lactam'' is a cyclic amide, and ''beta''-lactams are named so because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl. The simplest β-lactam possible is ...
antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...
is that of bacterial resistance. Prof Schofield is currently working on the design and synthesis of
enzyme inhibitor An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a sp ...
s for the metallo β-lactamases – there are no clinically used inhibitor of these enzymes but they pose a significant threat as they catalyse the hydrolysis of almost all clinically used
β-lactam A beta-lactam (β-lactam) ring is a four-membered lactam. A ''lactam'' is a cyclic amide, and ''beta''-lactams are named so because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl. The simplest β-lactam possible is ...
antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...
. A particular interest involves human metallo β-lactamases which share the same fold.


Awards and honours

2015-2020: Wellcome Trust Advanced Investigator Award (with Prof Sir Peter Ratcliffe) 2013:
Fellow of the Royal Society Fellowship of the Royal Society (FRS, ForMemRS and HonFRS) is an award granted by the judges of the Royal Society of London to individuals who have made a "substantial contribution to the improvement of natural knowledge, including mathemat ...
(London); Member of
EMBO Embo ( gd, Eurabol, IPA: ˆiaɾəpɔɫ̪ is a village in the Highland Council Area in Scotland and the former postal county of Sutherland, about north-northeast of Dornoch. On 16 July 1988, Embo declared itself independent from the rest of the ...
;
Fellow of the Royal Society of Biology Fellowship of the Royal Society of Biology (FRSB), previously Fellowship of the Society of Biology (FSB), is an award and fellowship granted to individuals that the Royal Society of Biology has adjudged to have made a "prominent contribution to ...
, UK; Member of the
Biochemical Society The Biochemical Society is a learned society in the United Kingdom in the field of biochemistry, including all the cellular and molecular biosciences. Structure It currently has around 7000 members, two-thirds in the UK. It is affiliated with th ...
; Member of the
Society for Experimental Biology The Society for Experimental Biology is a learned society for animal, cell and plant biologists. It was founded in 1923 at Birkbeck College to "promote the art and science of experimental biology in all its branches". It aims to demonstrate the i ...
, UK 2012: Finalist – Biotechnology and Biological Sciences Research Council 'Innovator of the Year' 2011:
Royal Society of Chemistry The Royal Society of Chemistry (RSC) is a learned society (professional association) in the United Kingdom with the goal of "advancing the chemical sciences". It was formed in 1980 from the amalgamation of the Chemical Society, the Royal Instit ...
, Jeremy Knowles Award, UK; Highly cited paper awards (''e.g.''
Biochemical Journal The ''Biochemical Journal'' is a peer-reviewed scientific journal which covers all aspects of biochemistry, as well as cell and molecular biology. It is published by Portland Press and was established in 1906. History The journal was established ...
, Bioorganic & Medicinal Chemistry Letters) 2009 – 2014: PI of ERC Advanced Investigator Grant SPA GA 2008 233240 (with Prof Sir Peter Ratcliffe); Molecular Mechanism of Oxygen Sensing by Enzymes (MOOSE) 2000:
Fellow of the Royal Society of Chemistry Fellowship of the Royal Society of Chemistry (FRSC) is an award conferred by the Royal Society of Chemistry (RSC) in the United Kingdom. FRSC award Achieving Fellow status in the chemical profession denotes to the wider community a high level of ...
(London)


References


External links

* http://schofield.chem.ox.ac.uk/ * http://research.chem.ox.ac.uk/christopher-schofield.aspx {{DEFAULTSORT:Schofield, Christopher J. 1960 births Alumni of St John's College, Oxford Alumni of the University of Manchester Institute of Science and Technology British chemists Fellows of Hertford College, Oxford Fellows of the Royal Society Fellows of the Royal Society of Chemistry People educated at St. Anselm's College Living people