Biography

Nigel Scrutton is Director of the Manchester Institute of Biotechnology (MIB) responsible for the strategic leadership and operational management of the institute, which comprises over 50 leading research groups from across all Faculties and is home to ca £100M of current grant funding and 8 spin out companies. 

Nigel has an established position in the field of enzyme catalysis, biophysics and biomolecular engineering. He holds an EPSRC Established Career Fellowship, is recipient of the Biochemical Society Colworth Medal, the RSC Charmian Medal, the RSC Rita and John Cornforth Award and a Royal Society Wolfson Research Merit Award. He has served on several national steering groups, advisory boards and governing bodies. He heads a group of ca 40 researchers. He has published ca 370 scientific papers, holds several patents, and has edited 3 volumes on enzyme chemistry, quantum biology, biocatalysis, synthetic biology and engineering. He has held contiguous externally funded research fellowships for 29 years (1988-2017) with only a 12-month break due to University relocation. Nigel is PI/Director of the BBSRC/EPSRC Synthetic Biology Research Centre 'SYNBIOCHEM' based in MIB. He is also PI/Director of a Marie Curie IDP 'MAGIC' responsible for the training of 12 early stage researchers at Manchester. Nigel is also a Director of the MIB spin out company C3 Biotechnologies Ltd. 

Nigel received a first class degree in Biochemistry, was awarded a Sambrooke Exhibition and the Robson Prize from the University of London, King's College. He gained his ScD and PhD (as a Benefactors' Scholar) at St John's College, the University of Cambridge. At Cambridge he was awarded the Henry Humphrey's Research Prize, held a Royal Commission for the Exhibition of 1851 Research Fellowship, a St John's College Research Fellowship and a Royal Society University Research Fellowship. He also held a Fellowship and was Director of Studies at Churchill College, University of Cambridge. In 1995 he moved to the University of Leicester as Royal Society University Research Fellow, where he later became Lister Institute Research Professor of Biochemistry and Professor of Biochemistry. He was appointed Professor at the University of Manchester in 2005, where he held a BBSRC Professorial Research Fellowship and was Associate Dean for Research prior to his appointment as MIB Director.

Nigel’s group is noted for its contributions to catalysis science, especially in the fields of quantum biology (tunnelling), dynamics and biocatalysis, and more recently synthetic biology. His work is interdisciplinary at the interfaces of chemistry, biology and physics, supported by a genuinely world-leading infrastructure for biophysical chemistry that he has established in MIB. 

Overview

Enzyme catalysts are central to life. They are the vehicles for delivering innovative bioscience solutions to chemicals manufacture, drug discovery, therapeutics and bioprocessing. They are the key enablers in the white biotechnology revolution, providing essential components in the new science of 'synthetic biology', offering new routes to biofuels, bulk and commodity chemicals and novel therapeutics. Despite this, our ability to create new enzymes through rational engineering is limited, which is a consequence of our poor understanding of mechanism and quantitative appreciation of the 'catalytic effect'. We are interested in gaining deeper understanding of catalysis and using this information to drive new applications. We focus on fundamental studies of enzyme mechanism, developing 'sharper' tools to analyse mechanisms across a wide range of timescales (femtoseconds to seconds). This involves both classical and quantum mechanical appreciation of the underlying chemistry. We then translate this knowledge into applications, e.g. in industrial biotechnology (chemicals manufacture), or development of potent inhibitors of enzyme function (drug discovery). Our work is highly interdisciplinary and we have broad interests captured by the descriptors: quantum biology; isotope effects; enzyme chemistry; laser spectroscopy; fast reactions methods; structural biology; kinetics and inhibition; enzyme evolution and pathway engineering; biocatalysis and biomanufacture.

Research interests

Biological catalysis, synthetic biology and biomolecular engineering.

I have been fascinated by the complexity and catalytic capabilities of enzymes throughout my career. My group has pursued research on the mechanisms and structures of biocatalysts - and more recently on light-responsive proteins - and integrated these studies into ambitious synthetic biology and metabolic engineering programmes (e.g. for chemicals production). At the basic discovery science end of the spectrum, my group has undertaken ambitious, wide-ranging interdisciplinary programmes in experimental enzyme biophysics and integrated these with structural and chemical biology, computational simulation and theory. Publications from the group reflect contributions from across these key discipline areas. Highlights have included demonstration of the unexpected importance of nuclear tunneling mechanisms in biological catalysis, discovery of new biological cofactors (e.g. prenylated flavins), structures of enzymes in complex with lead drug compounds (e.g. for Huntington's chorea/Alzheimer's disease) and mechanistic understanding of new roles for vitamin B12 and other photoreceptors in light-activated transcriptional regulation. In the fields of metabolic engineering/synthetic biology/directed evolution we have engineered organisms to biosynthesize propane gas and a wide array of monoterpenoid products. These programmes have their foundations in basic discovery science and in selected cases extend to commercial exploitation through spin out activity. We have established novel biophysics and synthetic biology infrastructure at Manchester to support this work including two major research centres in MIB: SYNBIOCHEM (Synthetic Biology Research Centre for Fine and Speciality Chemicals) and a biophysics facility (the Manchester Centre for Biophysics and Catalysis), which includes ultrafast laser UV, fluorescence up-conversion and IR spectroscopy as well as a suite of advanced time resolved spectoscopies for analysis of enzyme mechanisms. Given the breadth of the work in the group, we have a large research team (ca 40 staff) and strong collaborations with specialists in other disciplines (e.g. synthetic chemistry; materials science), both within MIB and external to Manchester.

Keywords: enzyme biocatalysts • quantum biology • quantum tunnelling • photochemistry • enzyme design • directed evolution • enzyme mechanisms • enzyme structures and dynamics • synthetic biology • chemicals biosynthesis • nanoscale bioengineering • biocatalysis • metabolic engineering

 

Teaching

Chemistry in the Life Sciences: A particular passion is 'putting the chemistry back into biochemistry' and moving away from  'blob-ology', i.e. the more descriptive view of biology. Life isn't about a series of interconnecting squares, triangles and circles in cellular communication networks (as is often depicted in text books and research papers) - its about chemistry. A complete understanding at the molecular level cannot happen without thorough grounding in chemical principles and knowledge of molecular structure, and students need to be comfortable in this space. Mechanistic and physical principles drive biological reactions, cell communication and replication and we cannot hope to understand biology at the systems or molecular levels without an understanding of the underlying key chemical and physical principles. Students must therefore not lose sight of the importance of chemical thinking to gain full appreciation of biological concepts.

Undergraduate: Mechanistic and molecular enzymology; enzyme kinetics and theory; fast reaction methods and spectroscopic studies of proteins; biophysical approaches to studies of protein systems; physical chemistry for biologists. 

Postgraduate: Experimental and theoretical approaches to studies of enzyme systems; structural and mechanistic enzymology; biocatalysis; physical principles underlying enzyme action; time resolved interrogation of enzyme mechanisms using multiple spectroscopies including ultrafast, laser photolysis, rapid mixing and equilibrium perturbation methods. Integration of structural and temporal data to elucidate and re-define enzyme function. Enzyme design/redesign, evolution and synthetic biology applications of enzymes (fuels; industrial chemicals; integrating chemo-biocatalysis).

Outreach: Outreach lectures 'World in Crisis' on catalysis and exploitation of enzymes in the modern world.

 

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