高宁

北京大学生命科学学院副院长

高宁，男，博士后，清华大学生命科学学院研究员，博士生导师。

教育经历

2000 学士北京大学生物化学及分子生物学系

2006 博士纽约州立大学Albany分校生物医学

工作经历

2017/4-，教授，北京大学生命科学学院

2017/4-，研究员，北京大学-清华大学联合生命中心

2008/11-2017/3，特别副研究员、助理教授、副教授（with tenure），教授，清华大学生命科学学院

2006-2008，博士后，纽约州Wadsworth Center，霍华德休斯医学研究所，哥伦比亚大学生化和分子生物物理系

荣誉奖励

2019 中组部第四批万人计划，科技创新领军人才

2018 科技部中青年科技创新领军人才

2018 教育部高等学校科学研究优秀成果奖—青年科学奖

2018 2017年度教育部长江特聘教授

2017 谈家桢生命科学创新奖

2017 国家自然科学基金杰出青年基金

2016 茅以升北京青年科技奖

2016 中源协和生命医学创新突破奖

2016 药明康德生命化学学者奖

2014 国家自然科学基金委优秀青年基金

2013 北京市高等学校青年英才计划

2006 Distinguished Doctoral Dissertation Award, SUNY at Albany

科研方向

高宁实验室主要致力于阐明细胞内大型蛋白-核酸复合物形成的分子机器的精细结构及工作分子机制，近年来的科研工作着重于核糖体的生物生成（ribosome biogenesis）、蛋白质生物合成的调控、DNA复制起始调控等重要基础生物学过程。实验室主要采用冷冻电镜三维重构的方法分析大型复合物的高分辨结构，辅助遗传学、细胞生物学、生化分子生物学手段回答大分子机器在功能执行过程中的机制性问题。同时，针对结构课题中的技术难点，实验室还致力于冷冻电镜方法学的研究，包括样品制备技术和算法的改进等。关注的一些基础生物学领域包括：

1. Ribosome biogenesis and translation regulation.

2. Structure and mechanisms of DNA replication machinery.

3. Structural and functional study of Long non-coding RNA.

运用冷冻电镜三维重构技术和生物化学及分子生物学手段进行生物大分子复合物的结构与功能研究。现有的工作重点包括原核和真核核糖体体内组装的机制和调控以及蛋白翻译的调控机制研究。

科学研究

2016年12月，高宁课题组和合作者在《Nature》（Doi:10.1038/nature20822）发表研究论文，报道了细菌中non-stop mRNA在核糖体上的翻译终止状态复合物的高分辨冷冻电镜结构，并揭示了ArfA在non-stop mRNA翻译终止过程中的作用机制；他们在体外组装了ArfA/RF2、non-stop mRNA、tRNA与70S核糖体的复合物，并获得了该复合物的高分辨冷冻电镜结构，结构表明ArfA C端的loop结合于核糖体30S小亚基上的mRNA进入通道，并占据了终止密码子的部分结合位点，而N端则直接与30S解码中心及RF2相互作用。进一步分析表明ArfA扮演了两个重要角色：N端作为mRNA长度的感受器，如果核糖体尚未行进到mRNA的3’末端，mRNA进入通道内的核苷酸会阻碍ArfA的结合；C端则通过和RF2直接结合，从功能上补偿了终止密码子对RF2的激活效应。该研究展示了具有极大结构柔性的小蛋白可以通过结构模拟来取代mRNA上的三碱基终止密码子的功能。

学术成果

1. Ma, C., Kurita, D., Li, N., Chen, Y., Himeno, H.#, and Gao, N.# (2017). Mechanistic insights into the alternative translation termination by ArfA and RF2. Nature 541, 550-553.

2. Ma, C., Wu, S., Li, N., Chen, Y., Yan, K., Li, Z., Zheng, L., Lei, J., Woolford, J.L., Jr.#, and Gao, N.# (2017). Structural snapshot of cytoplasmic pre-60S ribosomal particles bound by Nmd3, Lsg1, Tif6 and Reh1. Nat Struct Mol Biol 24, 214-220.

3. Zhai, Y., Cheng, E., Wu, H., Li, N., Yung, P.Y., Gao, N.#, and Tye, B.K.# (2017). Open-ringed structure of the Cdt1-Mcm2-7 complex as a precursor of the MCM double hexamer. Nat Struct Mol Biol 24, 300-308.

4. Li, N., Wu, J.X., Ding, D., Cheng, J., Gao, N.#, and Chen, L.# (2017). Structure of a Pancreatic ATP-Sensitive Potassium Channel. Cell 168, 101-110 e110.

· Recommended by “F1000”

5. Wu, S., Tan, D., Woolford, J.L., Jr., Dong, M.Q., and Gao, N.# (2017). Atomic modeling of the ITS2 ribosome assembly subcomplex from cryo-EM together with mass spectrometry-identified protein-protein crosslinks. Protein Science 26, 103-112.

6. Gu, J., Wu, M., Guo, R., Yan, K., Lei, J., Gao, N.#, and Yang, M.# (2016) Architecture of mammalian respirasome, Nature, 537, 639-643. DOI:10.1038/nature19359

· Recommended by “F1000”

7. Wu, S., Tutuncuoglu, B., Yan, K., Brown, H., Zhang, Y., Tan, D., Gamalinda, M., Yuan, Y., Li, Z., Jakovljevic, J., Ma, C., Lei, J., Dong, M.-Q., Woolford, J.L.#, and Gao, N.# (2016). Diverse roles of assembly factors revealed by structures of late nuclear pre-60S ribosomes. Nature 534, 133-137.

· Recommended by “F1000”, In F1000Prime, 13 Jun 2016; DOI: 10.3410/f.726394793.793519322.

8. Dong, D., Ren, K., Qiu, X., Zheng, J., Guo, M., Guan, X., Liu, H., Li, N., Zhang, B., Yang, D., Ma, C., Wang, S., Wu, D., Ma, Y., Fan, S., Wang, J., Gao, N., and Huang, Z. (2016). The crystal structure of Cpf1 in complex with CRISPR RNA. Nature 532, 522-526.

9. Ma, C., Yan, K., Tan, D., Li, N., Zhang, Y., Yuan, Y., Li, Z., Dong, M.Q., Lei, J., and Gao, N.# (2016). Structural dynamics of the yeast Shwachman-Diamond syndrome protein (Sdo1) on the ribosome and its implication in the 60S subunit maturation. Protein & Cell 7, 187-200.

10. Zhang, D., Yan, K., Liu, G., Song, G., Luo, J., Shi, Y., Cheng, E., Wu, S., Jiang, T., Lou, J., Gao, N. #, and Qin, Y.# (2016). EF4 disengages the peptidyl-tRNA CCA end and facilitates back-translocation on the 70S ribosome. Nat Struct Mol Biol 23, 125-131.

11. Zhang, J., Pan, X., Yan, K, Sun, S., Gao, N.# and Sui, S-F#. (2015). Mechanisms of ribosome stalling by SecM at multiple elongation steps. eLife, DOI: 10.7554/eLife.09684

12. Zhang, Y., Mandava, C.S., Cao, W., Li, X., Zhang, D., Li, N., Zhang, Y., Zhang, X., Qin, Y., Mi, K., Lei, J.#, Sanyal, S.#, and Gao, N.# (2015). HflX is a ribosome-splitting factor rescuing stalled ribosomes under stress conditions. Nat Struct Mol Biol 22, 906-913.

13. Zhang, D., Yan, K., Zhang, Y., Liu, G., Cao, X., Song, G., Xie, Q.#, Gao, N.#, and Qin, Y.# (2015). New insights into the enzymatic role of EF-G in ribosome recycling. Nucleic Acids Res 43, 10525-10533.

14. Ge, J., Li, W., Zhao, Q., Li, N., Chen, M., Zhi, P., Li, R., Gao, N.#, Xiao, B.#, and Yang, M.# (2015). Architecture of the mammalian mechanosensitive Piezo1 channel. Nature 527, 64-69.

15. Li, N., Zhai, Y.#, Zhang, Y., Li, W., Yang, M., Lei, J., Tye, B.K.#, and Gao, N#. (2015). Structure of the eukaryotic MCM complex at 3.8 A. Nature 524, 186-191.

· Highlighted in News & Views “DNA replication: Strand separation unraveled”;

· Recommended by “Faculty of 1000”, In F1000Prime, 19 Aug 2015; DOI: 10.3410/f.725681435.793508937

16. Zhang, Y., Ma, C., Yuan, Y., Zhu, J., Li, N., Chen, C., Wu, S., Yu, L., Lei, J.#, and Gao, N.# (2014). Structural basis for interaction of a cotranslational chaperone with the eukaryotic ribosome. Nat Struct Mol Biol 21, 1042-1046.

17. Zhang, X., Yan, K., Zhang, Y., Li, N., Ma, C., Li, Z., Zhang, Y., Feng, B., Liu, J., Sun, Y., Xu, Y., Lei, J.#, and Gao, N.# (2014). Structural insights into the function of a unique tandem GTPase EngA in bacterial ribosome assembly. Nucleic Acids Res 42, 13430-13439.

18. Feng, B., Mandava, C.S., Guo, Q., Wang, J., Cao, W., Li, N., Zhang, Y., Zhang, Y., Wang, Z., Wu, J., Sanyal, S.#, Lei, J.#, and Gao, N.# (2014). Structural and functional insights into the mode of action of a universally conserved Obg GTPase. PLoS Biol 12, e1001866.

· Highlighted in synopsis “Braking Bad: Stopping Translation in Hard Times”

19. Yang, Z., Guo, Q., Goto, S., Chen, Y., Li, N., Yan, K., Zhang, Y., Muto, A., Deng, H., Himeno, H., Lei, J.#, and Gao, N.# (2014). Structural insights into the assembly of the 30S ribosomal subunit in vivo: functional role of S5 and location of the 17S rRNA precursor sequence. Protein Cell 5, 394-407.

20. Liu, J., Mei, Z., Li, N., Qi, Y., Xu, Y., Shi, Y., Wang, F.#, Lei, J.#, and Gao, N.# (2013). Structural dynamics of the MecA-ClpC complex: a type II AAA+ protein unfolding machine. J Biol Chem 288, 17597-17608.

· Select by JBC editors as “Best Paper of the Year 2013” in molecular biophysics

21. Li, N., Chen, Y., Guo, Q., Zhang, Y., Yuan, Y., Ma, C., Deng, H., Lei, J.#, and Gao, N.# (2013). Cryo-EM structures of the late-stage assembly intermediates of the bacterial 50S ribosomal subunit. Nucleic Acids Res 41, 7073-7083.

22. Guo, Q., Goto, S., Chen, Y., Feng, B., Xu, Y., Muto, A., Himeno, H., Deng, H., Lei, J.#, and Gao, N.# (2013). Dissecting the in vivo assembly of the 30S ribosomal subunit reveals the role of RimM and general features of the assembly process. Nucleic Acids Res 41, 2609-2620.

23. Guo, Q., Yuan, Y., Xu, Y., Feng, B., Liu, L., Chen, K., Sun, M., Yang, Z., Lei, J.#, and Gao, N.# (2011). Structural basis for the function of a small GTPase RsgA on the 30S ribosomal subunit maturation revealed by cryoelectron microscopy. Proc Natl Acad Sci U S A 108, 13100-13105.

职务任免

2023年7月20日，北京大学生命科学学院新一届行政班子任命宣布会在金光生命科学大楼邓祐才报告厅召开，会上宣布任命高宁为副院长。

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