Objective The protein L-isoaspartyl methyltransferase (PIMT) is well known for its protein repair function, namely the reconversion of deamidated and/or isomerized asparaginyl and aspartyl residues (L-isoaspartyl residues) into their normal, non-isomerized forms. The conversion of biomolecules to non-useful and potentially toxic products by unwanted chemical reactions represents probably an important aspect of the aging process in living organisms. To the extent that they can minimize the accumulation of damaged molecules, they can endure. PIMT knockout mice accumulate high levels of damaged proteins in their tissues, especially the brain, and die of massive seizures at an average age of 42 days. On the other hand, worms and flies overexpressing this enzyme live longer, strongly suggesting a role for PIMT in the aging process. A particularly intriguing observation is that the insulin/IGF-1 signaling pathway is activated in the brain of PIMT knockout mice. Genetic evidence also exists for an interaction between PIMT and insulin-like signaling in Caenorhabditis elegans. It has recently become clear that insulin-like signaling plays an important role in the regulation of the aging process. Lowered insulin/IGF-1 signaling, especially in neuronal tissues, leads to lifespan extension in worms, flies and mice. The overall objective of this project is to understand the link between PIMT and insulin-like signaling. A first aim is to consolidate the interaction between PIMT and insulin-like signaling in worms. A second aim is to analyze the effect of PIMT deficiency on the phosphoproteome of mouse brains. A third aim is to elucidate the mechanism by which PIMT deficiency leads to the observed changes in protein phosphorylation. Several routes, including direct regulation of protein phosphatase activity by PIMT methylation, modulation of such an activity by a critical isoaspartyl residue, and effect of high isoaspartyl content in a protein on its phosphorylation state will be explored. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymesnatural scienceschemical sciences 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) Topic(s) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Call for proposal FP7-PEOPLE-2010-RG See other projects for this call Funding Scheme MC-IRG - International Re-integration Grants (IRG) Coordinator UNIVERSITE DU LUXEMBOURG EU contribution € 100 000,00 Address 2 PLACE DE L'UNIVERSITE 4365 ESCH-SUR-ALZETTE Luxembourg See on map Region Luxembourg Luxembourg Luxembourg Activity type Higher or Secondary Education Establishments Administrative Contact Alfred Funk (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Participants (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all DE DUVE INSTITUTE AISBL Participation ended Belgium EU contribution € 100 000,00 Address AVENUE HIPPOCRATE 75/50 1200 Bruxelles / Brussel See on map Region Région de Bruxelles-Capitale/Brussels Hoofdstedelijk Gewest Région de Bruxelles-Capitale/ Brussels Hoofdstedelijk Gewest Arr. de Bruxelles-Capitale/Arr. Brussel-Hoofdstad Activity type Research Organisations Administrative Contact Serge Thibaut De Maisières (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data