Project description DEENESFRITPL Advancing whole heart simulators It is well established that muscle contraction involves the cyclical interaction of myosin motors with actin filaments that lead to a sliding movement. The recently delineated mechanosensing (MS) mechanism active in the myosin thick filament addresses unresolved mechanistic gaps related to the fine regulation of muscle contraction. The scope of the EU-funded Heart Fi-Re project is to develop a mathematical model capable of quantitatively characterising the MS mechanism at the fibre level. The rationale is to incorporate this mechanosensing model into a powerful whole heart simulator and assess the macroscopic impact of the MS mechanism in various cardiomyopathies. Show the project objective Hide the project objective Objective 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. Fields of science natural scienceschemical sciencesinorganic chemistryalkaline earth metalssocial scienceslawnatural sciencesmathematicsapplied mathematicsmathematical model Keywords mechanosensing mechanism myosin regulation super-relaxed state Frank-Starling law heart simulator Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2019 - Individual Fellowships Call for proposal H2020-MSCA-IF-2019 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator UNIVERSITA DEGLI STUDI DI PADOVA Net EU contribution € 276 498,24 Address VIA 8 FEBBRAIO 2 35122 Padova Italy See on map Region Nord-Est Veneto Padova Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 276 498,24 Partners (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all Partner Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement. RIKEN THE INSTITUTE OF PHYSICAL ANDCHEMICAL RESEARCH Japan Net EU contribution € 0,00 Address HIROSAWA 2-1 351 0198 WAKO SHI SAITAMA See on map Activity type Research Organisations Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 184 761,60
