Studying the nanomechanics of hypertrophic cardiomyopathy

Nanomechanics of heart disease: investigating the effects of phosphorylation and HCM-causing mutations at the head-tail junction in cardiac myosin

Hypertrophic cardiomyopathy is a common disease of the heart muscle and detailed knowledge of the mechanism of heart contraction is central to design new therapies. Contractions arise from the molecular motions of a motor protein, myosin II, and are controlled by the RLC protein. Unfortunately, this system is difficult to study experimentally due to its size and the complexity of its motion. Dr Arianna Fornili has been awarded an Intermediate Basic Science Fellowship, during which she will work to overcome these limitations by combining computer modelling with a powerful experimental technique called Atomic Force Microscopy (AFM). In the laboratory as well as on the computer she will be able to apply forces to single molecules of the cardiac muscle and to understand how their motions change under normal and pathological conditions, that is when there are mutations in the regulatory protein RLC.