Objectif Cardiac connective tissue is regarded as passive in terms of cardiac electro-mechanics. However, recent evidence confirms that fibroblasts interact directly with cardiac muscle cells in a way that is likely to affect their beat-by-beat activity.To overcome limitations of traditional approaches to exploring these interactions in native tissue, we will build and explore murine models that express functional reporters (membrane potential, Vm; calcium concentration, [Ca2+]i) in fibroblasts, to identify how they are functionally integrated in native heart (myocyte => fibroblast effects). Next, we will express light-gated ion channels in murine fibroblast, to selectively interfere with their Vm (fibroblast => myocyte effects). Fibroblast-specific observation and interference will be conducted in normal and pathologically remodelled tissue, to characterise fibroblast relevance for heart function in health & disease.Based on these studies, we will generate 2 transgenic rabbits (fibroblast Vm reporting / interfering). Rabbit cardiac structure-function is more amenable to translational work, e.g. to study fibroblast involvement in normal origin & spread of excitation across the heart, in pathological settings such as arrhythmogenicity of post-infarct scars (a leading causes of sudden death), or as a determinant of therapeutic outcomes such as in healing of atrial ablation lines (interfering with a key interventions to treat atrial fibrillation).The final ‘blue-skies’ study will assess whether modulation of cardiac activity, from ‘tuning’ of biological pacemaker rates to ‘unpinning’ / termination of re-entrant excitation waves, can be achieved by targeting not myocytes, but fibroblasts.The study integrates basic-science-driven discovery research into mechanisms and dynamics of biophysical myocyte-fibroblast interactions, generation of novel transgenic models useful for a broad range of studies, and elucidation of conceptually new approaches to heart rhythm management. Champ scientifique natural scienceschemical sciencesinorganic chemistryalkaline earth metals 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) Thème(s) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Appel à propositions ERC-2012-ADG_20120314 Voir d’autres projets de cet appel Régime de financement ERC-AG - ERC Advanced Grant Institution d’accueil UNIVERSITAETSKLINIKUM FREIBURG Contribution de l’UE € 1 723 100,65 Adresse HUGSTETTER STRASSE 49 79106 Freiburg Allemagne Voir sur la carte Région Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Type d’activité Higher or Secondary Education Establishments Contact administratif Gerhard Henninger (Mr.) Chercheur principal Peter Kohl (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (2) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire UNIVERSITAETSKLINIKUM FREIBURG Allemagne Contribution de l’UE € 1 723 100,65 Adresse HUGSTETTER STRASSE 49 79106 Freiburg Voir sur la carte Région Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Type d’activité Higher or Secondary Education Establishments Contact administratif Gerhard Henninger (Mr.) Chercheur principal Peter Kohl (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE Participation terminée Royaume-Uni Contribution de l’UE € 775 511,75 Adresse SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON Voir sur la carte Région London Inner London — West Westminster Type d’activité Higher or Secondary Education Establishments Contact administratif Scott Wheatley (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
