Objectif Chronic heart failure is a leading cause of mortality in the industrialized countries. Pathomechanistically, a variety of diverse stress signals on the cardiomyocyte trigger loss of myofibrils and cardiomyocyte death, thereby activating a vicious cycle of cardiac stress and deterioration during terminal heart failure. Despite the enormous clinical relevance, the exact pathomechanisms in charge remains unclear.Here, I propose to investigate the molecular mechanisms that couple mechanical cardiomyocyte strain and cardiomyocyte loss during the heart failure involving the mechanosensing titin filament. For this, I will perform research in three globally leading teams and access their complementary expertise in a secondment scheme. In the the proposed 2-year outgoing phase, I will study how cardioprotection is mediated by key factors recently identified in the Ju Chen lab (UCSD, San Diego). During this time, I will be trained in cutting-edge molecular mouse genetic models and phenotyping tools. This research is expected to shed light on CARP-titinsignaling axis in cardiomyocyte death and to provide tools for manipulating this pathway. In a one-year re-integration phase I will perform follow-up mechanistic structural studies in the Olga Mayans lab (University of Liverpool) to determine the structural basis how the CARP (cardiac ankyrin repeat protein)-titin signaling axis mediates cardiomyocyte protection, and in the Labeit lab (University of Heidelberg, Medical Faculty Mannheim) how to perturb activity of this complex by small molecules.Taken together, this work encompasses structural studies at the atomic level up to vivo animal models to study CARP-titin functions. After the propose three years, I expect to be ready to pursue an independent career in the field of molecular cardiology research. Therefore, my goal during the re-integration phase will be to set-up an interdisciplinary collaboration involving the three lead teams of this proposal. Champ scientifique engineering and technologymaterials engineeringcrystalssocial sciencessociologydemographymortalitynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicinecardiologycardiovascular diseasesnatural sciencesbiological sciencesmolecular biology Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Thème(s) MSCA-IF-2014-GF - Marie Skłodowska-Curie Individual Fellowships (IF-GF) Appel à propositions H2020-MSCA-IF-2014 Voir d’autres projets de cet appel Régime de financement MSCA-IF-GF - Global Fellowships Coordinateur ZENTRALINSTITUT FUER SEELISCHE GESUNDHEIT Contribution nette de l'UE € 239 860,80 Adresse Square J 5 68159 Mannheim Allemagne Voir sur la carte Région Baden-Württemberg Karlsruhe Mannheim, Stadtkreis Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 239 860,80 Participants (1) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG Participation terminée Allemagne Contribution nette de l'UE € 0,00 Adresse SEMINARSTRASSE 2 69117 Heidelberg Voir sur la carte Région Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total Aucune donnée Partenaires (1) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire Partenaire Les organisations partenaires contribuent à la mise en œuvre de l’action, mais ne signent pas la convention de subvention. THE REGENTS OF THE UNIVERSITY OF CALIFORNIA États-Unis Contribution nette de l'UE € 0,00 Adresse FRANKLIN STREET 1111 12 FLOOR 94607 OAKLAND CA Voir sur la carte Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 160 130,40