Descrizione del progetto
Promuovere simulatori del cuore intero
È ben noto che la contrazione muscolare implica l’interazione ciclica dei motori della miosina con i filamenti di actina che portano a un movimento di scorrimento. Il meccanismo di meccanosensing (MS) recentemente delineato attivo nello spesso filamento di miosina affronta lacune meccanicistiche irrisolte legate alla regolazione fine della contrazione muscolare. L’ambito del progetto Heart Fi-Re, finanziato dall’UE, è quello di sviluppare un modello matematico in grado di caratterizzare quantitativamente il meccanismo di MS a livello di fibra. La logica è quella di incorporare questo modello di meccanosensing in un potente simulatore del cuore intero e valutare l’impatto macroscopico del meccanismo di MS in varie cardiomiopatie.
Obiettivo
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.
Campo scientifico
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP.
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP.
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
35122 Padova
Italia