Professor Yixiao Zhang’s long-term passion is to use single-particle cryo-EM to answer challenging mechanistic questions. Biological macromolecules are of fundamental importance for cell physiology. Studies aimed at elucidating the mechanisms underlying the biological functions of these biomacromolecules are thus key to our_­­_­ understanding of basic biological processes and how their dysfunction results in disease. The goal of structural biology is to visualize the architecture of biomacromolecules and to establish the molecular basis that enables them to perform their functions. 

While there has been tremendous progress in the use of single-particle Cryo-EM for structure determination, limitations and challenges remain. For example, it can be difficult to recapitulate the appropriate physiological environment for a protein and it can be exquisitely difficult to resolve the conformation of an underrepresented class of molecules in a structurally heterogeneous population. These issues impede the structural study of many important biomacromolecules. Professor Zhang has developed novel methods to mimic membrane tension to study mechanosensitive ion channels, and overcame numerous challenges on diverse biological samples, ranging from membrane proteins, protein-protein complexes, protein-RNA complexes to intact virus. These investigations elucidated several exciting and long-awaited functional mechanisms and resulted in several papers in top-tier journals, including Nature, Science, Molecular Cell, Nature Structural & Molecular Biology, Nature Communications, and PNAS.  

Currently Professor Zhang’s group is working on (1) mammalian mechanosensitive channels to understand the human sensations and other biological processes stimulated by mechanical force. (2) the machineries that involved in neurodegeneration and other diseases to understand their molecular mechanisms. (3) the biological processes that govern X-chromosome inactivation.