Abstract:
Single particle cryo-electron microscopy has undergone a revolutionary advance in resolving the biological structures of molecular machines at atomic resolution previously either difficult to attain or merely unachievable. It can also resolve structures of conformational or compositional heterogeneous molecular machines or biochemical reaction products at medium resolution. This achievement has owned to newly available direct electron detector to record electron images with enhanced signal to noise ratio at a full range of spatial frequencies and different image processing software contributed freely from many academic labs. Our Center has contributed to many of these advances including camera characterization, algorithm and software development for map and model determination and structure validation protocols. Recently, we have solved many cryoEM structures of molecular machines including viruses, chaperonins and transcriptional regulator not only in a single but also different biochemical states to uncover the structural mechanisms of their respective biological functions and assembly principles. Using cryo-electron tomography, we are able to generate 3-D images of protein aggregates and whole cells from bacteria to neurons and cancer cells where we can visualize the spatial and structural organization of subcellular components in both normal and diseased states. Novel structural features are discovered either to answer long standing mechanistic questions or to generate testable hypotheses for understanding structure and function relationship. Furthermore, cryo-electron tomography has the potential to become a structural biomarker for cancers and other diseases.
Brief Bio:
Professor Wah Chiu received his B.A degree in Physics from University of California, Berkeley. He also obtained his PhD in biophysics in 1975 from UC Berkeley. After staying at UC Berkeley for another four years, he joined University of Arizona to start his academic career and became a professor at Baylor College of Medicine in 1998. He is an elected academician of Academia Sinica, Taiwan and an elected member of National Academy of Sciences, USA.
Prof. Wah Chiu’s research interests are to determine 3-dimensional structures of biological nanomachines by electron cryomicroscopy and computer reconstruction and to relater the structures to their functional mechanisms. Our structural technique complements to those of X ray crystallography and NMR spectroscopy. Our laboratory is uniquely equipped with four intermediate voltage electron cryomicroscopes and supercomputer. His laboratory has pioneered various experimental and computational methods in biological cryo-EM.