Introduction

Research Groups

Select Research Group Head Prof. Sir Tom Blundell Prof. Kevin Brindle Dr Bill Broadhurst Dr Guy Brown Dr Mark Carrington Prof. Paul Dupree Prof. Gerard Evan - Head of Dept Prof. Richard Farndale Dr Giorgio Favrin Dr Jenny Gallop Dr Nick Gay Dr Andrew Grace Dr Jules Griffin Dr Brian Hendrich Dr Andrew Hesketh Dr Robin Hesketh Dr Matt Higgins Dr Florian Hollfelder Dr Hee-Jeon Hong Prof. Chris Howe Dr Marko Hyvonen Prof. Steve Jackson Dr Tony Jackson Prof. Richard Jackson Prof. Ernest Laue Prof. Peter Leadlay Dr Kathryn Lilley Dr Karen Lipkow Dr Rick Livesey Prof. Ben Luisi Dr Sarah Lummis Dr Juan Mata Dr John McCafferty Prof. Jim Metcalfe Dr Masanori Mishima Dr Eric Miska Dr Tom Monie Dr Helen Mott Dr Natasha Murzina Dr Daniel Nietlispach Dr Darerca Owen Prof. Steve Oliver Dr Luca Pellegrini Dr Markus Ralser Dr Nick Robinson Prof. George Salmond Dr Deirdre Scadden Dr José Silva Prof. Austin Smith Prof. Chris Smith Dr Nancy Standart Prof. Dame Jean Thomas Dr Aviva Tolkovsky Dr Martin Welch Dr Joyce Wong Dr Nianshu Zhang

Service & Research Support Facilities

Select by Subject or Manager DNA Sequencing Facility . . . . . Mr John Lester _______________________________ Quantitative Proteomics . . . . . Dr Kathryn Lilley _______________________________ Proteomics Core Services . . . . . Dr Mike Deery _______________________________ Protein & Nucleic Acid Chemistry . . . . . Dr Len Packman _______________________________ Metabolomics . . . . . Dr Jules Griffin _______________________________ Baculovirus Facility . . . . . Dr Darerca Owen _______________________________ Biophysics Facility . . . . . Dr Katherine Stott _______________________________ Crystallographic X-ray Facility . . . . . Dr Dima Chirgadze _______________________________ NMR spectroscopy . . . . . Dr Daniel Nietlispach _______________________________ Fermentation Facility . . . . . Dr Nianshu Zhang _______________________________ Bioinformatics & Computational Biology Services . . . . . Dr Jenny Barna _______________________________ Computer & IT Support . . . . . Dr Erik Timmers _______________________________

Past members last known active weblink

Select past member of Department Dr Stephen Bell Prof. Jonathan Blackburn Dr David Brown Dr Pak-Lee Chau Dr Hal Dixon (deceased) Dr Jessica Downs Prof. David Ellar Dr Paul Kemp Dr Simon Lovell Dr Kenji Mizuguchi Dr Massimo Paoli Prof. Richard Perham Dr Peter Reynolds Dr Philip Rubery Dr Gerry Smith Dr Margaret Sunde Prof. Jamie Vandenberg Dr Kira Weissman

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Structural Biology and Bioinformatics

Research Groupings: Structural and molecular cell biology | Developmental and regenerative biology and medicine

Tom Blundell completed his terms of thirteen years as Sir William Dunn Professor of Biochemistry and Head of Department and six years as Head of the School of biological Sciences on 30th September 2009. He was appointed Director of Research and Professor Emeritus. He continues to teach and conduct research in structural and computational biology and in drug discovery. In July 2009 he took up the post of Chair of the Biotechnology and Biological Sciences Research Council, a non-executive part-time appointment. He is also President of The Biochemical Society.

Research
Tom Blundell’s research is focused on structural biology and bioinformatics and their applications to drug discovery and medicine

Most of his work has been on multi-component protein assemblies – cell surface receptors and intracellular signal systems - that mediate cell regulation. In the 1960s and 1970s he became interested in the molecular structure and function of the hormones insulin, glucagon and oxytocin, but more recently has focused on growth factors including nerve growth factor (NGF), fibroblast growth factor (FGF) and hepatocyte growth factor/ scatter factor (HGF/SF) and their receptors. He has been particularly interested in the ways that multiprotein assemblies can achieve high signal to noise in Nature through cooperative interactions leading to specific but often transient assemblies.

Over the past decade he has extended his work on multiprotein systems to understanding DNA damage repair signaling, focusing on initially on homologous recombination (HR) in the study of Rad51 interactions with BRCA2, and more recently on Non-Homologous End Joining (NHEJ), both of which play major roles in double-strand break DNA repair. In NHEJ a ring-shaped Ku70/Ku80 heterodimer forms first at broken DNA ends, and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) binds to mediate synapsis. His group has recently reported a 3D structure of DNA-PKcs in complex with a fragment of Ku.  DNA ligase IV (LigIV) is recruited as a complex with XRCC4 for ligation, with XLF/Cernunnos, playing a role in enhancing activity of LigIV. They have used X-ray crystallography to determine structures of both XRCC4 and XLF. They are now using a combination of methods - X-ray crystallography, electron microscopy, small angle X-ray scattering, nanospray mass spectrometry, ITC and SPR - to gain insights the organisation of higher order complexes.

The group has developed widely used software in structural bioinformatics, including databases of three-dimensional structures of proteins (CREDO, PICCOLO, BIPA), software for sequence-structure (fold) recognition (FUGUE) and software for comparative modeling (COMPOSER, MODELLER, ORCHESTRAR, RAPPER). The current focus is on the identification and analysis of drug targets, especially those in Mycobacterium tuberculosis and Man, and on the analysis of the roles of nsSNPs and somatic mutations in human disease.

These interests have led to extensive work on structure-guided drug discovery. In the 1970s and 80s Tom Blundell focused on approaches to lead optimization, particularly antihypertensives targeted to renin, and AIDS antivirals, against HIV proteinase. In the past two decades he has become interested in fragment-based approaches to lead discovery, co-founding Astex Therapeutics and establishing academic groups in the University funded by the Bill and Melinda Gates Foundation, by the Wellcome Trust and by European Union, against both difficult targets (multiprotein systems) and neglected diseases (tuberculosis).

Lab members
Noha Abdel-Rahman, Michal Blaszczyk, Victor Bolanos-Garcia, Dimitri Chirgadze, Marcio Dias, Sungsam Gong, Alicia Higueruelo, Anjum Karmali, Semin Lee, Ann Ling, Bernado Ochoa Montano, Takashi Ochi, Will Pitt, Adrian Schreyer, Lynn Sibanda, Anna Sigurdardottir, Leonardo Silvestre, Jawon Song, Sachin Surade, Qian Wu.

References