Our main research interest lies in probing the structures of membrane proteins and their complexes, and understanding the molecular basis of their biological functions. My aim is to establish an infrastructure wherein the structure of any membrane protein including its complexes can be investigated in any functional state, i.e. catching molecular machines of cellular membranes in action.
Membrane proteins are involved in various critical biological processes, and account for 70% of all known pharmacological targets. However, only about 200 unique membrane protein structures have been identified because of the difficulty in forming crystals for X-ray and electron crystallography.
We have developed a novel and general method, called "random spherically constrained" (RSC) single-particle cryo-EM, to study membrane protein structures in membrane environments. The RSC method has involved the development of new specimen architectures and software algorithms that take advantage of these architectures, and has been successfully applied this method to obtain the structure of the large conductance voltage- and calcium-activated potassium (BK) channel in a lipid membrane, which answered several biologically important questions.