Description du projet
Faire progresser les simulateurs cardiaques complets
Il est bien établi que la contraction musculaire implique l’interaction cyclique des moteurs de la myosine avec les filaments d’actine qui entraînent un mouvement de glissement. Le mécanisme de mécanodétection (MdéfiniD) récemment , actif dans le filament épais de myosine, résout les lacunes mécanistes non résolues liées à la régulation fine de la contraction musculaire. Le champ d’application du projet Heart Fi-Re, financé par l’UE, consiste à développer un modèle mathématique capable de caractériser quantitativement le mécanisme de la MD au niveau des fibres. Son motif consiste à intégrer ce modèle de mécanodétection à un puissant simulateur cardiaque complet et à évaluer l’impact macroscopique du mécanisme de la MD dans différentes cardiomyopathies.
Objectif
Multi-scale heart simulators for patient specific treatments are an important challenge for the development of the health system, but require interdisciplinary interaction of several techniques to link experimental observations at the molecular level to the cardiac performance. The mechanosensing (MS) mechanism active in the myosin thick filament, recently discovered, is promising for the understanding of several unresolved questions in muscle field, including the molecular basis of the Frank-Starling law of the heart. MS mechanism finely regulates the number of myosin motors ready to generate force, sensing the tension sustained by the thick filament in any stage of the heart cycle. The mechanism appears to be crucial for the fine regulation of muscle contraction, deserving as a second regulator respect the classical Calcium concentration. However, its theoretical description at present is limited to purely phenomenological models and very few groups in the world are already able to produce clear evidences on it. The present project aims at establishing a collaboration between researchers in this field with complementary theoretical and experimental expertise to quantitatively characterize the MS mechanism at the fibre level through an innovative mathematical model and experimentally validate it with cutting-edge techniques present in the host and partner institutes. The fibre model will be included into a powerful whole heart simulator, to evaluate the macroscopic impact of MS mechanism, and its predicted effects on clinical problems, including its recently discovered relationships with cardiomyopathies. The project will foster an international network of collaborations, where the host institution will be a crucial node. The complimentary knowledges and high excellence of the groups, is a firm foundation on which to build the impact of the project: at my career level, at the institutes level and also at the system level.
Champ scientifique
CORDIS classe les projets avec EuroSciVoc, une taxonomie multilingue des domaines scientifiques, grâce à un processus semi-automatique basé sur des techniques TLN.
CORDIS classe les projets avec EuroSciVoc, une taxonomie multilingue des domaines scientifiques, grâce à un processus semi-automatique basé sur des techniques TLN.
Mots‑clés
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
35122 Padova
Italie