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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Regulation of Alternative Pre-mRNA Splicing

Research Groupings: Structural and molecular cell biology | Functional genomics, systems biology and genetic medicine

Our research focuses upon understanding the molecular basis of alternative pre-mRNA splicing. This is a process whereby individual genes are able to produce multiple mRNAs, often in a strictly cell-type or developmentally-regulated manner. It is a major form of gene regulation which helps to bridge the gap between the relatively limited number of genes in metazoan genomes and the far greater complexity of their proteomes. Indeed recent estimates indicate that the majority of human genes are alternatively spliced. Our group has used two major model systems to characterize the molecular mechanisms that regulate alternative splicing. The a-tropomyosin and a-actinin genes contain pairs of mutally exclusive exons, one of which is used widely in many cell types while the other is only selected in differential smooth muscle cells. A reversal of this splicing pattern accompanies the phenotype alterations of vascular smooth muscle cells that occur in atherosclerosis. The overall goal of the research is to characterize the factors that cause the switch of splicing pattern in smooth muscle cells and to understand their mode of action.

One of the splicing regulatory proteins in which we are interested, PTB, itself illustrates an important way in which alternative splicing can regulate gene expression without producing additional protein isoforms. This involves the production of RNAs that are substrates for the process of Nonsense Mediated Decay (NMD) rather than for translation. In the case of PTB an autoregulatory circuit involving alternative splicing directed NMD prevents accumulation of excessive amounts of PTB. We are currently engaged in investigating the prevalence and importance alternative splicing leading to NMD.

Lab members
Miguel Coelho, Christopher Edge, Clare Gooding, Martina Hallegger, Miriam Llorian, Jenny Reed, Lit Yeen Tan

References