Nieng Yan

Membrane transport is a vital physiological process that maintains cellular homeostasis, converts different energy forms, and generates and transduces signals. Transmembrane movement of chemicals can be achieved through diffusion, vesicular translocation, and protein-mediated facilitative diffusion or active transport. Based on the studies on representative channels, uniporters, and secondary active transporters, I seek to unveil the governing principles of membrane transport. The resolution revolution in cryo-electron microscopy (cryo-EM) has propelled structural biology into a new era. My scientific goal as a structural biologist is to reveal the molecular choreography at atomic resolution, to unveil the physiological and cellular processes involving membrane transport (including cellular uptake of glucose, generation of action potential, and excitation-contraction coupling of muscles). In the past five years, my laboratory has made significant progress towards elucidating the structures of human glucose transporters (GLUTs) and various eukaryotic voltage-gated sodium and calcium channels (Na_v and Ca_v). Moving forward, we aim to acquire their dynamic structures, to better comprehend how lipids modulate their activities, and to understand how disease-associated mutations cripple the normal functions of these membrane transport proteins . In addition, we plan to determine the atomic structures of recombinantly expressed and functionally well-characterized mammalian Na_v and Ca_v channels, in order to establish a consistent structure-function relationship. Finally, based on our previously resolve structures of endogenous Ca²⁺ channels (Ca_v1.1 and RyR1), we plan to employ cryo-electron tomography to resolve the in situ ultrastructure formed by plasma membrane-anchored Ca_v1.1 and sarcoplasmic reticulum-anchored RyR1, in an attempt to recapitulate excitation-contraction coupling of muscles with higher spatial and temporal resolutions. I believe that these studies will ultimately lead to the deciphering of the electromechanical coupling mechanism in cells, as well as structure-based drug discovery.