冷冻电镜三维重构作为结构生物学中的一项新技术，在生物大分子复合物的结构解析、结构动态变化研究等方面具有不可替代的作用，代表了生物物理领域的前沿。本项目申请人在博士和博士后期间学习于世界一流的冷冻电镜实验室，得到了全面系统的培训，积累了丰富的专业经验。在近十年的学习和研究工作中，采用冷冻电镜三维重构技术在核糖体的蛋白翻译、翻译调控、以及核糖体本身的生物合成等领域做出了重要的原创贡献，阐明了一系列的科学问题，工作成果发表于Molecular Cell、PNAS、Nucleic Acids Research、J. Mol. Bio.等多种国际期刊。本项目拟采用冷冻电镜单颗粒重构技术研究细胞内的一些重要的大分子复合物，包括真核和原核核糖体的生物合成、成熟及组装，蛋白翻译调控等过程，以及一些和疾病发生紧密相关的分子生物学过程。同时，针对结构解析中的难点问题，本项目还将积极开展相关的方法学研究。

As a novel and indispensable technique in the Structural Biology, cryo-electron microscopy (cryo-EM) is specialized in the 3D structural determination of large biological assemblies under near physiological condition, and especially, is well suited to study the structural dynamics of macromolecular complexes. The candidate has received solid and systematic cryo-EM training during his doctoral and post-doctoral study in a world-class cryo-EM lab, and has accumulated a wealth of skills and experiences in related field. In the past ten years, with this cutting-edge technique, the candidate has made a number of important contributions to the fields of ribosome structure, translation regulation, and ribosome biogenesis. These works were published in many prestigious international journals, such as Molecular Cell, PNAS, Nucleic Acids Research, and J. Mol. Bio. In this proposal, the candidate, on one hand, aims to use the cryo-EM and single-particle reconstruction techniques to study a few fundamental molecular processes in the cell, for examples, the dynamic process of the ribosome biogenesis, maturation and assembly, the regulated protein degradation, and molecular processes related to human diseases. On the other hand, along with the biological application of cryo-EM techniques, the candidate also aims at the methodological development, including improvements of current methods and new algorithm developments. Especially, we are interested in the further improvement of resolution for samples with low or no symmetry, and new image classification techniques for heterogeneous data.

冷冻电镜三维重构作为结构生物学中的一项新技术，在生物大分子复合物的结构解析、结构动态变化研究等方面具有不可替代的作用，代表了生物物理领域的前沿。课题组采用冷冻电镜三维重构技术在蛋白翻译调控、核糖体组装、DNA复制起始及大型膜蛋白复合物等领域做出了重要的原创贡献，阐明了一系列的科学问题，工作成果发表于Nature、Cell，Nature Structural and Molecular Biology，Molecular Cell、eLife、Nucleic Acids Research等多种国际期刊。同时，针对结构解析中的难点问题，课题组还开展了一些相关的方法学研究。