Objective 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. Fields of science natural sciencesbiological sciencesgeneticsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural scienceschemical sciencesanalytical chemistrymass spectrometrynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programme(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) Topic(s) ERC-SG-LS2 - ERC Starting Grant - Genetics,Genomics,Bioinformatics and Systems Biology Call for proposal ERC-2010-StG_20091118 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE EU contribution € 1 499 996,00 Address TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge United Kingdom See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments Administrative Contact Renata Schaeffer (Ms.) Principal investigator Markus Ralser (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE United Kingdom EU contribution € 1 499 996,00 Address TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments Administrative Contact Renata Schaeffer (Ms.) Principal investigator Markus Ralser (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data