Cardiac arrhythmias are on the rise in our aging population. They are electrical disturbances in the heart that can cause a wide variety of potentially life-threatening conditions, including an increased chance of stroke or, in the case of heart failure, sudden death. Anti-arrhythmic drugs that target a particular type of protein called an “ion channel” are useful in converting these irregular heart rhythms back to a normal beating. Unfortunately, many available anti-arrhythmic drugs have serious side effects. The basic action mechanisms of anti-arrhythmic drugs are not understood, and the chemical characteristics of good/safe anti-arrhythmic drugs are not known. This makes it difficult to engineer the next generation of life-saving cardiac drugs. Dr. Stephan Pless is aiming to fill crucial gaps in our understanding of how anti-arrhythmic drugs regulate heart function. By combining cutting-edge chemical methods with computer modeling, he has already made significant progress in defining the essential characteristics of what makes a “good” anti-arrhythmic drug. His next goal is even more important, as it aims to define the precise nature of the heart receptor through which anti-arrhythmic drugs modulate electric excitability. For this purpose, he will employ novel artificial amino acids to delineate the precise location of the receptor and will use novel fluorescent probes to give us insights into the atomic-level movements of the receptor during drug binding. All of the technologies used here have been tested in other relevant systems, but never for this application; therefore, it places Dr. Pless in a position to make a substantial contribution to the cardiovascular health of Canadians.