Abstract:

The ribosome is essential for protein biosynthesis in all living organisms. Functioning as a molecular machine with extraordinary size and complexity, it translates genetic information encoded in messenger RNA (mRNA) into functional proteins. Composed of ribosomal RNA (rRNA) and proteins, ribosomes consist of two subunits—large and small—that assemble around mRNA and interplay with various translation factors during translation. Although the atomic structure and basic function of the ribosome have been described for many prokaryotic and eukaryotic species, the regulation mechanisms mediated by various ribosome-binding proteins have just begun to unfold. The ribosome's absolute essentiality for cell growth has made it a prime target in the evolutionary arms race between bacteria and other microorganisms, particularly antibiotic-producing fungi. This has resulted in a wide array of natural antibiotics that specifically target the bacterial ribosome. Owing to the hyperactive activities of ribosome biogenesis and protein biosynthesis in cancer cells, a few natural products, such as those from plant and marine species, have been shown to have superior anti-ribosome activities and therapeutical potentials.

In this talk, I will provide a brief historical overview of ribosome structural studies, illustrating how our fundamental understanding of its function has continuously evolved in lockstep with groundbreaking technological innovations. I will then show an example from our lab: with the power of in situ cryo-electron microscopy, we have discovered an unprecedent mechanism of translation inhibition by a natural compound from algae, offering a novel atomic-level perspective on halting protein synthesis and opening new avenues for therapeutic design.

Profile

高宁，北京大学生命科学学院教授、副院长，膜生物学国家重点实验室副主任。2000年本科毕业于北京大学生命科学学院，2006年博士毕业于美国纽约州立大学奥尔巴尼分校。2006-2008年在哥伦比亚大学/HHMI从事博士后研究工作；2008-2017年任教于清华大学生命科学学院；2017至今任教于北京大学生命科学学院。实验室围绕着基础医学和生命科学中的科学问题，致力于与重大疾病发生发展相关的蛋白质复合物的结构和机制研究。近年来，实验室在超大生物分子复合物的组装和调控机制等领域取得系列进展，例如血红细胞膜骨架系统的组装和结构基础, 核糖体在细胞内组装的分子途径、组装因子的功能及机制，以及DNA复制起始过程的关键分子机器ORC、MCM等的工作机制。受聘为教育部 “长江学者奖励计划”特聘教授，获得国家杰出青年科学基金的资助，还获得了谈家桢生命科学奖、中源协和生命医学创新突破奖、药明康德生命化学奖、茅以升北京青年科技奖等奖励。