报告题目：Cryo-Electron Microscopy: From Visualizing Complex Dynamics to Therapeutic Discovery (冷冻电子显微镜：从复合动力学分析到靶向药物探索)
报告人：Prof. Youdong Mao (毛有东教授) (北京大学)
报告时间：2019年5月31日（周五） 下午15：00
报告地点：物理学院老楼一楼阶梯教室
Abstract:
Cryo-electron microscopy (cryo-EM) is transforming structural and chemical biology. The nature of cryo-EM single-particle images posits themselves being amenable to the theory and approaches previously developed for non-equilibrium statistical mechanics. Thus, it is possible that the principles and methodology in non-equilibrium statistical mechanics may transform the cryo-EM approach to enable its capability in solving complex dynamics of many-subunit system like 26S proteasome. In this talk, I will briefly outline the several lines of method development undergoing in my group that attempt to apply non-equilibrium statistical mechanical techniques to push the envelope of cryo-EM in analyzing extremely heterogenous systems at the atomic level. On the basis of these technological development, I will describe how we made several major breakthroughs in analyzing the substrate-degradation dynamics of human proteasome and in visualizing the intermediate NEK7-licensing step during NLRP3 inflammasome activation. These studies collectively highlight the ongoing transformation of cryo-EM from a key atomic imaging approach to an indispensable therapeutic discovery tool that might revolutionize molecular medicine in the future.
报告人简历：
毛有东，1977年4月出生于湖北荆州，1999年获武汉大学物理学学士，2005年获北京大学理学博士，师从欧阳颀院士。2005-2007年间，在国家纳米科学中心江雷院士课题组做项目博士后研究。2007-2015年间，在美国哈佛大学医学院先后任博士后，讲师（Instructor）和课题组长（Principal Investigator）。2015年回到北京大学物理学院工作。毛有东教授课题组主要从事软凝聚态、生物物理和化学生物学的交叉前沿研究和探索，尤其是发展并利用冷冻电子显微镜方法研究生物大分子机器和分子马达的结构动力学和非平衡统计物理基本规律，并试图应用于靶向分子设计。迄今为止，共发表论文46篇，通讯作者和第一作者论文26篇，累计影响因子320，其中16篇发表在影响因子不低于PNAS的学术期刊上，包括Nature（长论文2篇），Science（一篇），Nature子刊（3篇），Cell子刊（一篇）等。主持自主开发冷冻电镜并行计算软件ROME一套。获授权国家发明专利4项，国际发明专利2项，美国发明专利一项。受邀在国际国内学术会议做报告30多次。近期主要代表性论文：
1. Dong Y, Zhang S, Wu Z, Li X, Wang W, Zhu Y, Stoilova-McPhie S, Lu Y, Finley D, Mao Y*. Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome (Article). Nature 2019; 565:49-55.
2. Sharif H, Wang L, Wang WL, Magupalli VG, Andreeva L, Qiao Q, Hauenstein AV, Wu Z, Nunez G, Mao Y*, Wu H*. Structural mechanism for NEK7-licensed NLRP3 inflammasome activation (Article). Nature 2019; in press.
3. Dong Y, Chen S, Zhang S, Sodroski J, Yang Z, Liu D, Mao Y*. Folding DNA into a lipid-conjugated nanobarrel for controlled reconstitution of membrane proteins. Angew. Chem. Int. Ed. 2018; 57:2072-2076.
4. Chen S, Wu J, Lu Y, Ma YB, Lee BH, Yu Z, Ouyang Q, Finley D, Kirschner MW*, Mao Y*. Structural basis for dynamic regulation of the human 26S proteasome. Proc. Natl. Acad. Sci. USA 2016; 113:12991-12996.
5. Zhang L, Chen S, Ruan J, Wu J, Tong AB, Yin Q, Li Y, David L, Lu A, Wang WL, Marks C, Ouyang Q, Zhang X, Mao Y*, Wu H*. Cryo-EM structure of the activated NAIP2-NLRC4 inflammasome reveals nucleated polymerization. Science 2015; 350:404-409.
邀请人：王建波教授
