The Sun Group
The Sun Group aims to elucidate the molecular mechanisms of muscle contraction and its regulation at the single cell level. Despite increasingly detailed knowledge from work with isolated proteins about the molecular structure of troponin and other myofilament components, the complexity of the regulatory mechanism, and the interaction between proteins in the structurally-constrained myofibril, makes it difficult to extrapolate from these studies of isolated components. We determine molecular structural changes of muscle regulatory proteins in their native in situ complexes on the physiological timescale by a fluorescence polarisation technique (FISS, Fluorescence for In Situ Structure). Our current research activities have an emphasis on investigating the molecular mechanisms of heart muscle activation that underlie physiological and pathological modulation of myofilament Ca2+-sensitivity by β-adrenergic stimulation, cardiotonic drugs, and troponin mutations associated with cardiomyopathy. Understanding of these mechanisms will underpin the future development of new drugs and therapies for the wide range of cardiac diseases in which myofilament Ca2+-sensitivity is altered.
These works are in collaboration with Malcolm Irving (Randall Division, King's College London), David Trentham (Randall Division, King's College London) and Brian Skyes (University of Alberta, Canada) and are funded by BHF and MRC in the UK.
Figure: Regulatory domain of troponin moves dynamically during activation of cardiac muscle