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高宁

邮  箱: gaon@pku.edu.cn

职  称:教授

办公室电话:62744236

办公室地址:北京市海淀区颐和园路5号,北京大学,吕志和楼,100871

实验室电话:62744236

实验室地址:北京市海淀区颐和园路5号,北京大学,吕志和楼,100871

  • 个人简介
  • 科研领域
  • 代表性论文
  • 实验室简介

教育经历:

2001-2006,博士,生物医学系,纽约州立大学奥尔巴尼分校
1996-2000,学士,生命科学学院,北京大学

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

工作经历:

2017/4-至今,教授,北京大学生命科学学院
2017/4-至今,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
      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。
Ribosome Biogenesis and Translation Control

1. Li, Z., Ge, X., Zhang, Y., Zheng, L., Sanyal, S.#, and Gao, N.# (2018). Cryo-EM structure of Mycobacterium smegmatis ribosome reveals two unidentified ribosomal proteins close to the functional centers. Protein & Cell 9, 384-388.
2. Zhang, Y., Xiao, Z., Zou, Q., Fang, J., Wang, Q., Yang, X.#, and Gao, N.# (2017). Ribosome Profiling Reveals Genome-wide Cellular Translational Regulation upon Heat Stress in Escherichia coli. Genomics, Proteomics & Bioinformatics 15, 324-330.
3. Li, Z., Guo, Q., Zheng, L., Ji, Y., Xie, Y.-T., Lai, D.-H., Lun, Z.-R., Suo, X., and Gao, N.# (2017). Cryo-EM structures of the 80S ribosomes from human parasites Trichomonas vaginalis and Toxoplasma gondii. Cell Research 27, 1275-1288.
4. Biedka, S., Wu, S., LaPeruta, A.J., Gao, N., and Woolford, J.L., Jr. (2017). Insights into remodeling events during eukaryotic large ribosomal subunit assembly provided by high-resolution cryo-EM structures. RNA Biol 10, 1306-1313.
5. 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.
6. 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.
7. Kong, M.Y., Yan, K.G., Ma, C.Y., and Gao, N. # (2016). Distinct Binding and Enzymatic Activities of Two Ribosome-dependent NTPases YchF and YihA. Progress in Biochemistry and Biophysics 43, 570-578.
8. Tutuncuoglu, B., Jakovljevic, J., Wu, S., Gao, N., and Woolford, J.L., Jr. (2016). The N-terminal extension of yeast ribosomal protein L8 is involved in two major remodeling events during late nuclear stages of 60S ribosomal subunit assembly. RNA 22, 1386-1399.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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
14. 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.
15. 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.
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.
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. 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.
21. 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.
22. 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.
23. Gao, N., Zavialov, A.V., Ehrenberg, M., and Frank, J. (2007). Specific interaction between EF-G and RRF and its implication for GTP-dependent ribosome splitting into subunits. J Mol Biol 374, 1345-1358.
24. Frank, J., Gao, H., Sengupta, J., Gao, N., and Taylor, D.J. (2007). The process of mRNA-tRNA translocation. Proc Natl Acad Sci U S A 104, 19671-19678.
25. Gao, N., and Frank, J. (2006). A library of RNA bridges. Nat Chem Biol 2, 231-232.
26. Gao, N., Zavialov, A.V., Li, W., Sengupta, J., Valle, M., Gursky, R.P., Ehrenberg, M., and Frank, J. (2005). Mechanism for the disassembly of the posttermination complex inferred from cryo-EM studies. Mol Cell 18, 663-674.

DNA Replication, Epigenetic Regulation & other Protein-RNA/DNA complexes

1. Yan, L., Wu, H., Li, X., Gao, N.#, and Chen, Z. # (2019). Structures of the ISWI-nucleosome complex reveal a conserved mechanism of chromatin remodeling. Nat Struct Mol Biol 10.1038/s41594-019-0199-9. (在线发表)
2. Li, N., Lam, W.H., Zhai, Y.#, Cheng, J., Cheng, E., Zhao, Y., Gao, N.#, and Tye, B.K.# (2018). Structure of the origin recognition complex bound to DNA replication origin. Nature 559, 217-222.
3. Zhai, Y.#, Li, N., Jiang, H., Huang, X., Gao, N.#, and Tye, B.K.# (2017). Unique Roles of the Non-identical MCM Subunits in DNA Replication Licensing. Molecular Cell 67, 168-179.
4. 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.
5. 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.
6. Peng, R., Xu, Y., Zhu, T., Li, N., Qi, J., Chai, Y., Wu, M., Zhang, X., Shi, Y., Wang, P.#, Wang, J.#, Gao, N.#, and Gao, G.F.# (2017). Alternate binding modes of anti-CRISPR viral suppressors AcrF1/2 to Csy surveillance complex revealed by cryo-EM structures. Cell Research 27, 853-864.
7. 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.

Membrane Protein Complex & other Large Molecular Machines

1. Jiang, F., Li, N., Wang, X., Cheng, J., Huang, Y., Yang, Y., Yang, J., Cai, B., Wang, Y.P., Jin, Q.#, and Gao, N.# (2019). Cryo-EM Structure and Assembly of an Extracellular Contractile Injection System. Cell 10.1016/j.cell.2019.02.020. (在线发表)
2. Liang, K., Li, N., Wang, X., Dai, J., Liu, P., Wang, C., Chen, X.W., Gao, N., and Xiao, J. (2018). Cryo-EM structure of human mitochondrial trifunctional protein. Proceedings of the National Academy of Sciences of the United States of America 10.1073/pnas.1801252115.
3. Yu, J., Zhang, B., Zhang, Y., Xu, C.Q., Zhuo, W., Ge, J., Li, J., Gao, N.#, Li, Y.#, and Yang, M.# (2018). A binding-block ion selective mechanism revealed by a Na/K selective channel. Protein & Cell 9, 629-639.
4. Yuan, Y., Du, C., Sun, C., Zhu, J., Wu, S., Zhang, Y., Ji, T., Lei, J., Yang, Y., Gao, N.#, and Nie, G.# (2018). Chaperonin-GroEL as a Smart Hydrophobic Drug Delivery and Tumor Targeting Molecular Machine for Tumor Therapy. Nano Lett 18, 921-928.
5. Zhang, S., Li, N., Zeng, W., Gao, N.# and Yang, M.# (2017). Cryo-EM structures of the mammalian endo-lysosomal TRPML1 channel elucidate the combined regulation mechanism. Protein & Cell 8, 834-847.
6. 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.
7. Gu, J., Wu, M., Guo, R., Yan, K., Lei, J., Gao, N.#, and Yang, M.# (2016) The architecture of mammalian respirasome, Nature, 537, 639-643.
8. 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.
9. Sun, C., Yuan, Y., Xu, Z., Ji, T., Tian, Y., Wu, S., Lei, J., Li, J.#, Gao, N.#, and Nie, G#. (2015). Fine-tuned H-ferritin nanocage with multiple gold clusters as near-infrared kidney specific targeting nanoprobe. Bioconjugate chemistry 26, 193-196.
10. 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.

实验室近年来主要关注蛋白翻译的调控机制研究。作为分子生物学中心法则的一个重要环节,蛋白翻译是细胞内的基因表达调控网络的一个重要组成部分。高等生物的翻译调控机制的诸多细节还尚不清楚,例如数量庞大的通过遗传和生化手段鉴定的核糖体结合因子是如何结合到核糖体、翻译因子或者mRNA上,是如何在分子水平上参与翻译本身及其调控。除此之外,核糖体本身的组装和成熟,也是基因表达调控的一项主要全局调控模式,与细胞的生长、增殖、分化及个体的发育密切相关。实验室的重要长期目标就是关注这些科学问题的解答。例如,以酿酒酵母为模式系统,实验室在国际上首次获得了定位于细胞核内的真核核糖体组装前体的原子分辨率结构,阐释了多种功能各异的核糖体组装因子的可能分子功能


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