Interview with Dr. Wei Yang, 2022 Keynote Speaker, American Chemical Society Division of Chemical Toxicology.

Interview with Dr. Wei Yang, 2022 Keynote Speaker, American Chemical Society Division of Chemical Toxicology.
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专访美国化学会化学毒理学部 2022 年主题演讲人杨伟博士。

DOI:
10.1021/acs.chemrestox.2c00313
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发表时间:
2022
影响因子:
4.1
通讯作者:
Conlon,SavannahG
Conlon,SavannahG
中科院分区:
医学3区
文献类型:
--
作者:
Conlon,SavannahG

文献摘要

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杨伟博士在 2022 年秋季的 ACS TOXI 会议上发表了鼓舞人心的主题演讲。在解决了多种 DNA 修复蛋白的结构超过 25 年后,她以一句具有挑衅性的引言作为演讲的开场白:“结构生物学不仅仅是一张静态的图片;相反,我们试图让它变得生动和动态。”杨博士的实验室采用多方面的方法不仅研究DNA错配和核苷酸切除修复,还研究跨损伤合成和V(D)J重组。事实上,她的演讲重点关注了她和她的实验室赋予生命的各种蛋白质,这些蛋白质确实令人着迷。讨论的主要话题是杨博士实验室提出的酶催化理论的修订,该理论是三金属离子依赖性的,而不是广泛接受的双金属离子催化机制。利用时间分辨 X 射线晶体学,杨博士的团队已经能够识别出酶功能所必需的瞬时填充的第三金属位点。这已在多种 DNA 关联蛋白中得到报道,包括她演讲中提到的三种:DNA 聚合酶 η、核酸内切酶 V 和 RNase H1。她用一个类比来解释三金属离子催化理论。就撑杆跳而言,一个人能跳多高是有限制的。与酶促反应类似,酶的功能最终会受到限制,这与双金属离子催化类似。然而,“第三种金属离子”就像给了撑竿跳高运动员一根棍子,这样他就可以更有效地越过撑杆。杨就读于纽约州立大学石溪分校,并获得了生物化学学士学位。随后,她在哥伦比亚大学韦恩·亨德里克森博士的指导下获得了硕士和博士学位,并在他的实验室获得了博士后职位。随后,她在耶鲁大学跟随诺贝尔奖获得者 Thomas A. Steitz 博士完成了第二次博士后研究。她从 1995 年开始成为 NIH 的终身研究员。她在 NIH 工作了 25 年多,现在是一名杰出研究员。杨博士因其在DNA修复领域的开创性贡献而获得多个奖项,包括2011年的Dorothy Crowfoot Hodgkin奖和2017年的Mildred Cohn生物化学奖。她于2013年和2015年被提名并当选为著名的美国国家科学院院士和美国艺术与科学院院士。杨博士谈到了是什么激励她追求科学。当她还是个在中国上海长大的孩子时,她一直认为成为一名科学家是遥不可及的。她梦想成为像爱因斯坦或牛顿那样的人,能够做出原本可能不会受到关注的发现。
Dr. Wei Yang presented an inspiring keynote talk for the ACS TOXI meeting this Fall 2022. She opened her talk with a provocative quote after solving the structures of multiple DNA repair proteins over 25 years:“Structural biology is not just a static picture; instead, we try to make it vivid and dynamic.” Dr. Yang’s laboratory uses a multifaceted approach to study not only DNA mismatch and nucleotide excision repair but also translesion synthesis and V (D) J recombination. Indeed, her talk focused on the various proteins she and her laboratory have brought to life and was truly captivating. The main topic of discussion was the revised theory of enzyme catalysis which Dr. Yang’s laboratory proposes to be threemetal-ion dependent rather than the widely accepted twometal-ion catalysis mechanism. Using time-resolved X-ray crystallography, Dr. Yang’s group has been able to identify a transiently populated third metal site that is necessary for enzyme function. This has been reported in multiple DNA associating proteins, including the three touched on in her talk: DNA polymerase η, endonuclease V, and RNase H1. She gave an analogy to explain the three-metal-ion catalysis theory. In the case of pole vaulting, there is a limit to how high a man can jump; similar to enzymatic reactions, there eventually is a limit to enzyme function, and this is the analogy to two-metal-ion catalysis. However, the “third metal ion” is like giving the pole vaulter a stick so he can get over the pole that much more efficiently.Dr. Yang attended State University of New York at Stony Brook where she received her bachelor’s degree in Biochemistry. She then went on to receive her MS and Ph. D. degrees under Dr. Wayne Hendrickson at Columbia University, followed by a postdoctoral position in his laboratory. She then completed her second postdoctoral fellowship with Nobel Laureate Dr. Thomas A. Steitz at Yale University. She became a tenure-track investigator at NIH starting in 1995. She has worked at the NIH for over 25 years and is now a Distinguished Investigator. Dr. Yang has received several awards for her groundbreaking contributions to the field of DNA repair, including the Dorothy Crowfoot Hodgkin Award in 2011 and the Mildred Cohn Award in Biological Chemistry in 2017. She was nominated and elected to the prestigious National Academy of Sciences in 2013 and American Academy of Arts and Sciences in 2015. Dr. Yang spoke about what inspired her to pursue science. When she was a child growing up in Shanghai, China, she always thought being a scientist was unachievable. She dreamed of being like Einstein or Newton who could make discoveries which might not have received attention otherwise.