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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Molecular Assembly Lines and Combinatorial Biosysnthesis

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

Polyketide natural products such as the antibiotic erythromycin A, the immunosuppressant rapamycin, or the anticancer compound geldanamycin, are synthesised on giant multienzyme assemblies whose size rivals or exceeds that of the ribosome. We aim to understand the structure of these polyketide synthases (PKSs) and the mechanism of polyketide chain assembly and the further enzymatic tailoring of the products using a wide range of genetic, enzymological and protein engineering approaches. We are also exploring the creation of hybrid multienzymes capable of producing novel analogues of important polyketide drugs.

Our current projects include: (1) detailed mechanistic analysis of ketosynthase, ketoreductase, acyltransferase and dehydratase enzymes from PKSs, their protein engineering and directed evolution; (2) design and assembly of novel PKSs in order to produce rare anticancer polyketides of marine origin; and (3) detailed functional analysis of a large number of novel PKS clusters to deepen our understanding of the potential of these systems for synthetic biology. As an example, we are collaborating with the group of Stewart Cole (Institut Pasteur, Paris) to analyse the remarkable polyketide synthases that produce mycolactone, a highly toxic polyketide implicated in the emerging disease known as Buruli ulcer, which may lead to more effective therapies. We are also interested in novel ways of identifying the intracellular protein targets of such polyketide drugs and toxins.

Lab members
Matt Biancalana, Naomi Bossley, Reda Deglau, Yuliya Demydchuk, Anna Efimova, Qinxhi Fan, Andrew Gallimore, Frank Hahn, Hui Hong, Michael Kenning, David Kwan, Orestis Lazos, John Lester, Markiyan Samborskyy, Frank Schulz, Nataliya Scott, Yuhui Sun, Manuela Tosin, Lucky Tran, Shu Wu

References