Getting FISSical to understand heart muscle contraction

In situ structural studies of the role of sarcomeric proteins in the regulation of heart muscle

Each heart beat is triggered by a pulse of calcium in a heart muscle cell, and is driven at the molecular level by myosin and actin filaments sliding past each other and generating the force for contraction. Calcium triggers contraction by binding to regulatory molecules that block the interaction of actin and myosin – when calcium binds, structural changes take place so actin and myosin can interact. Although the sequence of events that lead to heart muscle contraction are well described, we still don’t completely understand exactly how these protein-protein interactions occur and what feedback loops control these processes. In this Senior Basic Science Research Fellowship, Dr Yin-Biao Sun at King’s College London will use his expertise in biophysics to examine how the myofilament proteins (actin, myosin and regulatory proteins) work together to effect contraction and relaxation of heart muscle during the heart beat, and what goes wrong in conditions like cardiomyopathy, where the myofilament proteins are mutated. He will use a new fluorescence technique that he has helped to establish at King’s called fluorescence for in situ structure (FISS) to measure structural changes in the regulatory proteins during contraction of heart muscle cells under normal conditions or conditions that mimic disease. The results will help us understand how the heart muscle is activated by calcium, how the actions of the regulatory proteins are modified in heart disease, and how to design drugs to control these changes.