Clarke Lab

The ultimate goal of the research of the Clarke Lab is a structural understanding of how the voltage gated Ca2+ channels on the plasma membrane mechanically couple to the ryanodine receptor and directly control gating of the receptor, and how adjacent RyRs in the paracrystalline arrays that have been observed at the terminal cisternae interact with one another and signal cooperatively. Intracellular calcium signaling, mediated by release of calcium from intracellular stores, is involved in many fundamental biological processes, amongst which perhaps most prominent is the coupling of nervous excitation to muscle contraction (E-C coupling). A key goal of the Clarke Lab is to understand the mechanism by which intracellular calcium release is triggered, modulated, and terminated. We use X-ray crystallography and cryoelectron microscopy (CryoEM) to investigate the structure and dynamics of the molecular machines involved in such process, including, amongst others, the ryanodine receptor (RyR), which mediates intracellular Ca2+ release during E-C coupling.