Dual-filament regulation optimises the performance of heart muscle During each heartbeat, the myosin motors on the thick filament generate force and shortening by interacting with overlapping actin filaments and using as fuel the ATP produced by the cardiac cell. Instead, during heart filling the motors are packed in an OFF state which inhibits their ATP consumption. The research in the lab is focused on the regulatory system in the cardiac thick-filament that constantly adapts the number of motors that are in the OFF or ON state and is responsible for the graded control of strength and duration of contraction of the cardiac muscle. When this regulation system fails motors are released inappropriately from the OFF state causing an energy imbalance in the heart which possibly leads to the development of cardiomyopathies. We combine structural techniques at the cellular level to study the OFF-to-ON transition of the myosin motors in beating cardiac muscle cells.