What goes wrong with the heart’s beat in heart disease?

Dual-filament regulation optimises the performance of heart muscle

Dr Elizabetta Brunello at King’s College London is working out how protein ‘motors’ within heart muscle cells make heart cells contract, by travelling up and down muscle filaments, like trains travelling along tracks. She wants to understand how this intricate process is controlled, and what goes wrong in heart disease. During each heartbeat, the ‘myosin’ motors on the thick muscle filament generate force by interacting with overlapping ‘actin’ filaments – which act like scaffolding within cells. They use a molecule called ATP as a fuel. When the heart relaxes between beats and fills with blood again, the motors switch off, stopping them from using ATP. Dr Brunello is studying the regulatory system controlling the number of motors switched off or on, which determines the strength and duration of heart muscle contraction. When this regulatory system fails, motors turn on at the wrong time, causing an energy unbalance in the heart, and potentially leading to diseases called cardiomyopathies. In this project, Dr Brunello will study how the myosin motors switch from ‘off’ to ‘on’ when the heart muscle contracts using beating heart muscle cells, and how the number of active motors changes to control heart contraction. This research will reveal more about how the heartbeat is controlled, what goes wrong in heart disease, and new ways to treat it.