Objetivo The metabolic network has a modular architecture, is robust to perturbations, andresponds to biological stimuli. The balance of the network, and the passageway ofnetwork substructures to operate at different activity, requires intensive interactionsbetween the metabolic network, the transcriptome and the proteome. However, thebiochemical mechanisms monitoring the metabolic network are only barely understood.Changes in network activity are often mediated through so called reporter metabolites:general -network interconnecting cofactors and reaction substrates - and specific pathwayintermediates. These metabolites bridge the gap between the small molecule andmacromolecular universe of the cell.Here we propose combining systematic yeast genetics with targeted metabolomics andproteomics to understand mechanisms of metabolic regulation on a genome-scale level. Inprinciple, we will elaborate multiple reaction monitoring (MRM) assays that facilitatequantification of enzymes and intermediates of selected metabolic pathways via liquidchromatography tandem mass spectrometry. The analysis will be performed on metabolicprocesses that influence aging; those will be analyzed and the results validated bychemical-genetic profiling and competitive lifespan experiments.The anticipated results will yield in a system-wide picture of interactions between themetabolome and regulatory components of the cell. Furthermore, it will identify novelgenetic and biochemical interactions of the aging process. Understanding thesemechanisms will stimulate new research directions in Systems Biology and support thedevelopment of therapeutic strategies against diseases of aging. Ámbito científico natural sciencesbiological sciencesgeneticsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural scienceschemical sciencesanalytical chemistrymass spectrometrynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programa(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) ERC-SG-LS2 - ERC Starting Grant - Genetics,Genomics,Bioinformatics and Systems Biology Convocatoria de propuestas ERC-2010-StG_20091118 Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-SG - ERC Starting Grant Institución de acogida THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Aportación de la UE € 1 499 996,00 Dirección TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Reino Unido Ver en el mapa Región East of England East Anglia Cambridgeshire CC Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Renata Schaeffer (Ms.) Investigador principal Markus Ralser (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Reino Unido Aportación de la UE € 1 499 996,00 Dirección TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Ver en el mapa Región East of England East Anglia Cambridgeshire CC Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Renata Schaeffer (Ms.) Investigador principal Markus Ralser (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos