Objectif The aim of this proposal is to characterize the metabolic impact of the expression of key transcripts involved in fatty acid metabolism by using the model organism Caenorhabditis elegans. In particular, the main focus of the project will be on the systemic manipulation of the expression of genes for the fatty acid desaturases by an RNAi based intervention to understand their key role as regulatory control points in metabolism. To achieve this aim we will make use of state of the art metabolomic approaches including Nuclear Magnetic Resonance (NMR) spectroscopy, Gas Chromatography Mass Spectroscopy (GC-MS) and Liquid chromatography Mass Spectrometry (LC-MS) to provide a global, non-targeted description of systemic metabolism. Metabolomic analysis, conducted on different genetically modified animals, will result in a rich data-base of metabolomic profiles that, with the help of multivariate data analysis techniques, will permit the identification of specific biochemical markers that determine which pathways have been perturbed. In addition, we will also analyze flux changes directly using stable isotope labelled substrates experiments. The combination of steady state concentration data and flux changes will provide a description of the reorganization of the metabolism following the targeting of a given gene by our RNAi based intervention. Overall, the results will allow a global insight into consequences of altered genetic expression across the whole system of metabolism without any loss of intrinsic complexity - a so-called top-down systems biology approach. In addition understanding the metabolic roles the desaturases play in regulating global lipid metabolism will help us to increase our understanding of human metabolic diseases associated with lipid metabolism dysfunction including obesity, type II diabetes, dyslipidaemia and the metabolic syndrome. Champ scientifique natural sciencescomputer and information sciencesdata sciencenatural sciencesbiological sciencesgeneticsnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsnatural scienceschemical sciencesanalytical chemistrymass spectrometrynatural sciencesphysical sciencesopticsspectroscopy Mots‑clés C Metabolomics NMR MS diabetes elegans fatty acid metabolism Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-IEF-2008 - Marie Curie Action: "Intra-European Fellowships for Career Development" Appel à propositions FP7-PEOPLE-IEF-2008 Voir d’autres projets de cet appel Régime de financement MC-IEF - Intra-European Fellowships (IEF) Coordinateur THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Contribution de l’UE € 171 867,63 Adresse TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Royaume-Uni Voir sur la carte Région East of England East Anglia Cambridgeshire CC Type d’activité Higher or Secondary Education Establishments Contact administratif Edna Murphy (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
