Scheme: Wolfson Research Merit Awards
Organisation: University of Bristol
Dates: May 2011-Apr 2016
Summary: My main focus is on understanding how cardiac contraction comes about and why it becomes compromised in disease. I use a variety of biophysical, biophotonic, computational and cell biological approaches to clarify how electrical excitation leads to calcium release inside the cell. This key mechanism has resisted out understanding for more than 130 years -since calcium was discovered to be a major regulator of the heart beat. My discovery of ‘calcium sparks’ provided a part of the solution, but how a calcium spark was terminated to allow relaxation of the muscle has been a major stumbling block for the past 20 years. We have shown that the key to the problem appears to reside in the molecular gating patterns of the individual ion channels that release calcium from the internal stores. These gating patterns coupled with the geometry of the cellular organization of the calcium release channels allows the calcium-induced calcium release process to automatically stop via a mechanism we have called ‘induction decay’. This key insight will provide much needed information for the development of new types of therapy for diseases where the calcium release mechanism becomes faulty.