Obiettivo 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. Campo scientifico natural scienceschemical sciencesinorganic chemistryalkaline earth metals Programma(i) 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) Argomento(i) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Invito a presentare proposte ERC-2012-ADG_20120314 Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-AG - ERC Advanced Grant Istituzione ospitante UNIVERSITAETSKLINIKUM FREIBURG Contributo UE € 1 723 100,65 Indirizzo HUGSTETTER STRASSE 49 79106 Freiburg Germania Mostra sulla mappa Regione Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Gerhard Henninger (Mr.) Ricercatore principale Peter Kohl (Prof.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (2) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto UNIVERSITAETSKLINIKUM FREIBURG Germania Contributo UE € 1 723 100,65 Indirizzo HUGSTETTER STRASSE 49 79106 Freiburg Mostra sulla mappa Regione Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Gerhard Henninger (Mr.) Ricercatore principale Peter Kohl (Prof.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE Partecipazione conclusa Regno Unito Contributo UE € 775 511,75 Indirizzo SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON Mostra sulla mappa Regione London Inner London — West Westminster Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Scott Wheatley (Mr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato
