Descripción del proyecto
Hacer avanzar los simuladores de corazón completo
Es bien sabido que la contracción muscular implica la interacción cíclica de los motores de miosina con filamentos de actina que conducen a un movimiento deslizante. El mecanismo de mecanodetección recientemente definido y activo en el filamento grueso de miosina aborda cuestiones mecánicas no resueltas relacionadas con la regulación fina de la contracción muscular. El objetivo del proyecto Heart Fi-Re, financiado con fondos europeos, es desarrollar un modelo matemático capaz de caracterizar cuantitativamente el mecanismo de mecanodetección a nivel de las fibras. La idea es incorporar este modelo de mecanodetección a simuladores potentes de corazón completo y evaluar el impacto macroscópico del mecanismo de mecanodetección en varias miocardiopatías.
Objetivo
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.
Ámbito científico
CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural.
CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural.
Palabras clave
Programa(s)
Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
35122 Padova
Italia