Understanding the role of myosin super relaxation in cardiac health and disease

The heart circulates blood by the coordinated contractions of the cells of the heart. The contraction of these cells is driven by myosin, a molecular motor which uses cellular energy. ~70% of myosin molecules in the heart are in an 'off' state. This 'off' state allows the heart to conserve energy. 'Off' myosin can be turned 'on' depending on how hard the heart needs to beat, but how this is done by the cell is not fully understood. In some inherited heart conditions, myosin is not able to switch off, due to mutations in a person's DNA, which can cause heart failure. The amount of myosin in the 'off' state may also change in many common heart conditions including atrial fibrillation and heart failure. I aim to understand how the myosin 'off' state is regulated so that we can design new therapies for patients with heart conditions.