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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Applications of Metabolomics to Disease and Regulation of Metabolism

Research Grouping: Functional genomics, systems biology and genetic medicine | Cardiovascular science and medicine

Larger version of this figure Figure 1: An orthogonal signal corrected Partial Least Squares-Discriminate Analysis plot of various mouse models of cardiac disease using solution state NMR spectroscopy to measure the metabolome of the heart in each case. Key: control mice, + mdx mouse (model of Duchenne muscular dystrophy), model of cardiac hypertrophy (MLPKO), model of cardiac arrhythmia (Scn-/+), , model of cardiac arrhythmia (ScnΔ/+) .

In the post-genomic era, there is an increased drive towards an understanding of the functional effects of a given gene. Metabolomics is the large-scale analysis of metabolites, and this process of generating a metabolic profile to follow a pathophysiological insult or stimulus has been highly successful at distinguishing the effects of genetic modifications and disease states in a range of organisms, including man. We are using high resolution 1H Nuclear Magnetic Resonance (NMR) spectroscopy and Mass Spectrometry in conjunction with pattern recognition techniques to define metabolic profiles characteristic of the disease/pathology being investigated. The group has access to world class facilities in metabolomics including a 500 MHz NMR spectrometer, a Thermo LTQ ion trap, a Waters QTOF Ultima, a Waters Quattro Premiere triple quadrupole LCMS and two GC-MS. Our group is currently involved in a number of integrated genomic and metabolomic studies.

A metabolomic investigation of type II diabetes, obesity and the metabolic syndrome: We have been using a combination of animal models (mouse, rat and more recently C.elegans) to understand the metabolic consequences of the diseases that make up the metabolic syndrome including type II diabetes, obesity, fatty liver disease and dyslipidaemia. In addition we have cross-correlated metabolomic data with proteomics and transcriptomics to build up a “systems biology” description of the consequences of pathology and genetic modulation related to the metabolic syndrome.

Metabolomic studies of cancer: We have investigated the metabolic changes that accompany the formation and death of a range of different cancers both in cell systems and whole organisms. This has included investigating metabolic changes associated with non genotoxic carcinogenicity and lipid metabolism during apoptosis in tumours. We are also involved in a EU Framework 7 project to investigate biomarkers associated with different classes of breast tumours.

Figure 2: High resolution 1H NMR spectra of extracts of liver tissue from the PPAR-alpha knock-out mouse. In this mouse the hepatic concentration of glucose and glycogen markedly decrease with time as the liver shows evidence of hepatic steatosis. Larger version of this figure

Lab members
Zsuzsanna Ament, Cecilia Castro, Kian Kai Cheng, Martin Coleston, Susan Connor, Melanie Gulston, Mark Hodson, Chen Juan-Lu, Steven Murfitt, Lee Roberts, Denis Rubtsov, Reza Salek, Baljit Ubhi, Aalim Weljie, James West

References