Grant: Operating Grant

Heart disease is the leading cause of death of men and women in Canada, and results in the highest economic burden to our health care system. While death rates from heart disease in Canada have fallen over the last 10 years, the good news is offset by the fact that heart disease is affecting more women, and becoming more prevalent as a complication of diabetes and obesity. The role of the cardiac muscle proteins in heart disease is being recognized as clinical evidence indicates a strong correlation between many cardiac dysfunctions and altered myofilament protein structures. For example, mutations of myofilament proteins have been associated with familial hypertrophic cardiomyopathy; one of the most frequently occurring inherited disease that often cause sudden cardiac death in young healthy athletes. This proposal is focused on the elucidation of the detailed mechanism of the regulation of cardiac muscle contraction. Only then can we truly understand how cardiac muscle works. We use high resolution NMR spectroscopy to determine the three dimensional structures of the calcium regulatory proteins, to delineate their interactions with other proteins as well as cardiotonic drugs, and to evaluate the effects of mutations on their structure. The outcome of this research is a detailed understanding at a molecular level, which can then be exploited to rationally design and develop possible therapeutic intervention strategies and advanced diagnostics for the treatment of heart disease.