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 Pathogenesis of Cardiac Arrhythmias

Research Groupings: Cardiovascular science and medicine | Metabolic medicine, integrative and comparative physiology

Most of our research involves the characterisation of the molecular basis of the heart beat and the substrates that are responsible for cardiac arrhythmias. A central aim is to test the hypothesis that changes in ion channel function and/or expression are important in the pathogenesis of arrhythmias. Initially the studies have focused on monogenic ion channel disorders but have developed to include genetically complex cardiac disease.

Arrhythmias arise when the normal processes of cardiac excitation break down. They provide useful experimental insights into how the heart should function and are usually due to re-entrant waves of excitation, the conditions for which are favoured by slowed intraventricular conduction and delayed repolarization. These parameters are measured using computer-driven stimulation protocols derived from our clinical work applied in genetically modified (GM) animal models.

The work is highly integrated and moves from the identification and characterization of novel ion channel and receptor genes through functional analysis using gene-targeting to the invasive analysis of cardiac arrhythmia substrates in patients. The fact that measurements made in humans can be also be obtained in GM mice highlights the translational aspects of the approach. Our most recent work has described the mechanisms of cardiac arrhythmogenesis in a series of novel GM mice with targeted disruptions in respectively the potassium channel gene, KCNE1, and the sodium channel gene, Scn5a, with work in progress on the ryanodine receptor, RyR2. We have also initiated a large-scale genomics project looking at the genetic basis of sudden cardiac death with the Wellcome Trust Sanger Institute. In addition clinical trials of biophysical measurements from the human heart, 'fractionation', in patients at possible risk of sudden cardiac death continue across Europe. Together these provide the background to the refinement of the basic science programme leading to a much better understanding of the genetic basis of sudden cardiac death, its mechanisms, prediction and prevention.

Lab members
Yana Dautova, Nina Ghais, Iman Gurung, Parvez Hakim, Sandeep Hothi, Chris Huang, Matthew Killeen, Thomas Pedersen, Gary Tse, Yanmin Zhang, Yanhui Zhang

References