Pioneers: Academic Career in Cryo-EM Structural Biology

I established my independent laboratory in 1989 at the Department of Biological Sciences and Biotechnology (which was renamed the School of Life Sciences in 2009) at Tsinghua University. Since 1991, I have held a professorship at Tsinghua University for more than three decades. My laboratory was one of the earliest in China to apply three-dimensional electron microscopy to the study of the structures of biological macromolecules. In the 1990s, my laboratory primarily focused on the two-dimensional crystallization of proteins on lipid monolayer and their structural studies using electron microscopy. By the late  1990s, our laboratory gradually shifted towards structural research using the single-particle electron microscopy technique. A representative achievement of this period was the elucidation of the transition of the protease DegP between a cage-like oligomer in solution and a bowl-shaped oligomer on membrane surfaces. Following the resolution revolution in cryo-electron microscopy, we determined the high-resolution structure of an 18-megadalton phycobilisome in 2017-marking the first near-atomic model of this giant complex since its discovery half a century ago. In recent years, we have focused on in situ high-resolution structure determination and method development. In 2023, we reported a near-atomic resolution in situ structure of the phycobilisome-photosystem membrane protein megacomplex,determined from cellular lamellae.