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Structural and Functional Systems

Overview

The Structural and Functional Systems research group brings together researchers interested in understanding biology at the molecular level, linking structure with function. Research in the group spans the kingdoms of life investigating the molecular basis of virus, plant, microbial, animal and human biology. It often uses an interdisciplinary approach combining the use of structural biology with advanced enzymological, spectroscopic or computational studies.

Research group leader: Prof David Leys

Members

  • Andrew Almond - The role of molecular dynamics in extracellular matrix organisation
  • Johanna Avis - Protein and RNA structure-function relationships
  • Jordi Bella - Structure of collagen and extracellular matrix proteins
  • Ewan Blanch - Application of Raman spectroscopies to biological molecules
  • Andrew Doig - Amyloidosis and protein folding
  • Bob Ford - Membrane protein structural biology
  • Alexander Golovanov - Structural studies of biological molecules using NMR spectroscopy
  • Sam Hay - Biophysics and quantum biology
  • Simon Hubbard - Computational biology related to proteomics and genomics
  • Giles Johnson - Regulation of electron transport processes in response to stress
  • David Leys - Protein structure and function
  • Andrew Munro - Molecular enzymology of cofactor binding proteins
  • Steve Prince - Membrane Protein Structural Biology
  • Steve Rigby - Biological electron magnetic resonance
  • Alan Roseman - Cryo-electron microscopy
  • Nigel Scrutton - Enzyme biophysics, structure and mechanism
  • Paul Sims - Molecular parasitology of malaria
  • Jon Waltho - Amyloid-fibril formation, phosphoryl transfer enzyme mechanism
  • Jim Warwicker - Models for structural cell biology
  • Michael White - Systems biology analysis of signaling, transcription and cell fate

Affiliates

  • Clair Baldock - Structural studies on microfibrillar components of the extracellular matrix
  • Caroline Bowsher - Plant carbohydrate metabolism and nitrate assimilation
  • Tony Day - Protein-polysaccharide interactions in inflammatory processes
  • Jeremy Derrick - The structural biology of cell surface proteins in bacterial pathogens
  • Karl Kadler - Tendon development, biomechanics and repair
  • Simon Lovell - Evolution of protein structure
  • Hui Lu - Import, folding and assembly of mitochondrial proteins
  • Jean-Marc Schwartz - Pathways and biological systems modelling
  • Lydia Tabernero - Structural biology of protein phosphatases and signalling proteins
Electron density of a P450 heme group.

Electron density of a P450 heme group.

Mobile flavin domain of ETF in complex with a protein partner.

Mobile flavin domain of ETF in complex with a protein partner.

Bipartite interaction network of drugs and therapies.

Bipartite interaction network of drugs and therapies.

Cover illustration of surface enhanced Raman optical activity.

Cover illustration of surface enhanced Raman optical activity.

Contrasting responses of photosynthesis to salt stress.

Contrasting responses of photosynthesis to salt stress.

pH-dependence of conductance in the Kv1 family of potassium channels.

pH-dependence of conductance in the Kv1 family of potassium channels is predicted to depend on specific residue pairings.

Cover picture illustrating transcriptional regulation of halorespiration.

Cover picture illustrating transcriptional regulation of halorespiration.

Substrate channelling in bifunctional enzymes.

Substrate channelling in bifunctional enzymes.

The molecular basis of pH-dependent binding of TSG-6 to hyaluronan.

Cover picture illustrating the molecular basis of pH-dependent binding of TSG-6 to hyaluronan.

Peptides identified by mass spectrometry mapped back to the genome.

Peptides identified by mass spectrometry mapped back to the genome.

 

About us

The SFS groups contains two Royal Society University Research Fellows, David Leys and Hui Lu.

Recent grant award: David Leys obtained a prestigious ERC starting grant to investigate the basis of halorespiration.

Together with other investigators from Manchester, Nigel Scrutton and David Leys were awarded the 2009 Rita and John Cornforth Award RSC team-award.

Recent grant award: Simon Hubbard and others have been awarded £3 million to analyse the entire protein content of 'baker's yeast' and further understanding of how living cells function.

Andy Almond is one of the finalists for the BBSRC Innovator of Year Award 2009.

Nigel Scrutton and John McCarthy are recipients of a prestigious BBSRC Professorial Fellowship.

The total annual research grant income of the SFS group is in excess of £4.7 million.

Papers published by members of the SFS research group have been cited over 45000 times.

Recent appointments: Steve Rigby and John Waltho have recently joined the university and add considerable strength and spectroscopy expertise to the SFS group.

Andrew Munro and Simon Hubbard are core members of the recently installed Research Committee D (Molecules, cells and industrial biotechnology) of the BBSRC.

Recent grant award: Andy Munro and David Leys obtained an BBSRC Industrial Partnership award with DSM Delft to work on Pravastatin synthesis.

 

Spotlight on...

RNA interacting proteins

Professor Simon Hubbard and Dr Paul Sims together with Drs Graham Pavitt, Mark Ashe and Chris Grant have been awarded £2,847,862 by BBSRC to fund a study entitled "Understanding how RNA interacting proteins modulate the translatability of mRNAs".

Previous work shows that, when stressed, yeast cells down-regulate the translation of most genes. However, hundreds of individual mRNAs resist this global trend, demonstrating an additional level of control important for determining how such mRNAs respond to stress conditions. Using yeast cells exposed to specific stresses, the goal is to define these novel mechanisms of translational control. Experimentally, the proposal is to conduct a large genome-wide study to characterise both regulated mRNAs and the protein partners that mediate their control in response to three different stress regimens.

simon.hubbard@manchester.ac.uk

3D and 4D structures of a small soluble molecule

Andrew Almond's spin-off company Conformetrix is going from strength to strength. Conformetrix offers a new platform technology that, for the first time, can rapidly determine highly accurate and biologically-relevant (aqueous) 3D and 4D structures of any small soluble molecule. Its proprietary method quantifies experimentally the 4D conformational preference (in terms of modality, angle and libration amplitude) of each rotatable bond without recourse to electrostatics or van der Waals calculations. Conformetrix structures can be used to advantage within existing research and development infrastructures in pharmaceutical, agrochemical, petrochemical, food additive and cosmetics industries.

http://www.conformetrix.com/

RNA iF1000 logo

Recent F1000 BIOLOGY selected papers

Cobalamin uptake and reactivation occurs through specific protein interactions in the methionine synthase-methionine synthase reductase complex.
Wolthers KR, Scrutton NS
FEBS J 2009 Apr 276(7):1942-51

Nuclear Quantum Tunneling in the Light-activated Enzyme Protochlorophyllide Oxidoreductase.
Heyes DJ, Sakuma M, de Visser SP, Scrutton NS
J Biol Chem 2009 Feb 6 284(6):3762-7

Molecular basis of halorespiration control by CprK, a CRP-FNR type transcriptional regulator.
Levy C, Pike K, …, van der Oost J, Leys D
Mol Microbiol 2008 Aug 20

RECENT APPOINTMENT

ENDOR pH titration of a flavoenzyme

Steve Rigby - The main theme of my research is the study of free radicals and transition metal ions in biological systems using spectroscopic techniques. Free radicals and transition metal ions are found naturally at the active sites of many enzymes, alternatively they can be inserted as 'artificial' probes of structure and function. I specialise in the 'electron magnetic resonance' (EMR) techniques electron paramagnetic resonance (EPR) spectroscopy and electron nuclear double resonance (ENDOR) spectroscopy. The key to extracting biologically relevant information from such experiments is to combine the spectroscopy with appropriate biological perturbations. Most experiments involve a close association between biology and spectroscopy, often to the point where the division between the two disciplines vanishes.

stephen.rigby@manchester.ac.uk

The Molecular Enzymology Group

Molecular enzymology

The Group is based within the new state-of-the-art research centre, the Manchester Interdisciplinary Biocentre (MIB), and comprises a number of independent but highly complementary research groups who broadly tackle a number of key questions regarding the structures and mechanisms of enzymes. They take a multidisciplinary approach using fast reaction kinetic and spectroscopic methods, X-ray crystallography, NMR, computational chemistry, protein engineering and chemistry to seek a detailed understanding at the atomic level of how enzymes 'work'. With this knowledge enzymes can be developed as drug targets, manipulated for use in biotechnology/biocatalysis or used to further our general understanding of various processes in biology and chemistry.

The Molecular Enzymology Group

Structural and functional genomics of Mycobacterium tuberculosis

As part of an EU network, Structural and functional genomics of Mycobacterium tuberculosis (X-TB), Andrew Munro is studying the worldwide threat to human life that Mtb presents. Novel intervention strategies are desperately needed to avert what the World Health Organization describes as a potential “global catastrophe”. Azole drugs are potent antituberculars, and typically target cytochrome P450 enzymes by inactivating their function. We have solved crystal structures of key mycobacterial P450s and established their functional role, providing critical data for design of novel antitubercular therapeutics.

andrew.munro@manchester.ac.uk

RITA AND JOHN CORNFORTH AWARD

Photo of the Tunnelling team

Congratulations to the “Tunnelling team”
Nigel Scrutton, David Leys, Mike Sutcliffe, Sam Hay, Chris Pudney, Linus Johannissen, Jiayun Pang and Derren Heyes are the first winning team of the RSC Rita & John Cornforth Award (previously the Chemistry Biology Interface Forum Team Award). This award rewards scientists working in collaborative research teams with both chemistry and the life sciences disciplines. The tunnelling team work has focused on studying the quantum mechanical behaviour of H-atoms in enzymes. Detailed investigations into this process require the interdisciplinary collaboration the team now routinely undertakes.

Rita and John Cornforth Award