Grants awarded

Thick filament-based mechanisms for the dynamic regulation of contraction and relaxation in the heart

Grantholder:

Dr Luca Fusi

King's College London

United Kingdom

During each heartbeat the myosin motors on the thick filament use ATP as a fuel to generate force by interacting with overlapping actin filaments, while during heart filling the myosin motors are switched off to inhibit ATP consumption. Dynamic regulation of the number of motors in the off or on state is essential for the graded control of strength and duration of contraction of the cardiac muscle. Defects in this dynamic regulation lead to reduced cardiac output and heart failure.

My research is focused on the regulatory systems in the thick filament that control the on/off state of the myosin motors during the heartbeat. I will use structural techniques at cellular and sub-cellular level to find out how the dynamic regulation of the myosin motors in the on or off state control the speed of contraction and relaxation in cardiac muscle.

My findings will help us understand the regulation systems that control heart muscle.