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高宁

  • 教授
  • 北京大学生命科学学院副院长
    膜生物学国家重点实验室北大分室主任
    北京大学-清华大学生命科学联合中心
    北京大学国家生物医学成像科学中心（兼）
    多模态跨尺度生物医学成像设施装置负责人
  • 个人简介
    实验室围绕着生命科学的核心内容，主要运用冷冻电镜技术研究与重大生命过程相关的分子机器的结构和功能，探索重要的基础生物学机制问题及相关的人类重大疾病的发生机制。近年来,实验室的科研工作聚焦于核酸-蛋白复合物分子机器及组成复杂的大型蛋白复合物。实验室的重要研究领域包括：
    （1）病原体的核糖体是很多抗菌药物的天然靶点，同时人源核糖体生物生成（ribosome biogenesis）也在多种人类肿瘤细胞中异常上调，并且和肿瘤转移的能力正相关。实验室以细菌、酵母、人源细胞系作为模型，研究人类病原体、模式生物以及人类核糖体的生物组装机制，不同核糖体结合蛋白在蛋白翻译中的新颖调控功能和分子机制，以及潜在药物靶标的发现；
    （2）DNA复制是分子生物学的核心环节，DNA复制的紊乱也是众多肿瘤的一项标志性特征。实验室研究真核生物DNA复制起始过程的蛋白质分子机器的结构和工作机制；
    （3）实验室同时也和众多课题组紧密合作，包括临床科学家，研究人类重大疾病治疗靶点的结构和机制。
  • 获奖及荣誉
    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 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
  • 个人履历
    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
    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
  • 团队成员
    李宁宁副研究员
    秘书：刘洋
  • 承担项目
    基金委重点项目、杰青项目等
  • 代表性论文及论著
    1. Chen, Y., Tsai, B., Li, N., and Gao, N.# (2022). Structural remodeling of ribosome associated Hsp40-Hsp70 chaperones during co-translational folding. Nature communications 13, 3410.
    2. Cheng, J., Li, N., Huo, Y., Dang, S., Tye, B.-K.#, Gao, N.#, and Zhai, Y.# (2022). Structural Insight into the MCM double hexamer activation by Dbf4-Cdc7 kinase. Nature communications 13, 1396.
    3. Ma, C., Wang, C., Luo, D., Yan, L., Yang, W., Li, N., and Gao, N. (2022). Structural insights into the membrane microdomain organization by SPFH family proteins. Cell Res 32, 176-189.
    4. Yang, F., Guo, L.L., Li, Y., Wang, G.P., Wang, J., Zhang, C., Fang, G.X., Chen, X., Liu, L., Yan, X., et al. (2021). Structure, function and pharmacology of human itch receptor complexes. Nature 600, 164-169.
    5. Zheng, L., Zheng, Z., Li, X., Wang, G., Zhang, K., Wei, P., Zhao, J.#, and Gao, N#. (2021). Structural insight into the mechanism of energy transfer in cyanobacterial phycobilisomes. Nature communications 12, 5497.
    6. Zheng, L., Liu, Z., Wang, Y., Yang, F., Wang, J., Huang, W., Qin, J., Tian, M., Cai, X., Liu, X., Mo, X., Gao, N.#, and Jia, D.# (2021). Cryo-EM structures of human GMPPA-GMPPB complex reveal how cells maintain GDP-mannose homeostasis. Nat Struct Mol Biol 28, 1-12.
    7. Zhao, T., Chen, Y.M., Li, Y., Wang, J., Chen, S., Gao, N.#, and Qian, W.# (2021). Disome-seq reveals widespread ribosome collisions that promote cotranslational protein folding. Genome Biol 22, 16.
    8. Micic, J., Li, Y., Wu, S., Wilson, D., Tutuncuoglu, B., Gao, N.#, and Woolford, J.L., Jr.# (2020). Coupling of 5S RNP rotation with maturation of functional centers during large ribosomal subunit assembly. Nature communications 11, 3751.
    9. Wilson, D.M., Li, Y., LaPeruta, A., Gamalinda, M., Gao, N.#, and Woolford, J.L., Jr.# (2020). Structural insights into assembly of the ribosomal nascent polypeptide exit tunnel. Nature communications 11, 5111.
    10. Liang, X., Zuo, M.Q., Zhang, Y., Li, N., Ma, C., Dong, M.Q., and Gao, N.# (2020). Structural snapshots of human pre-60S ribosomal particles before and after nuclear export. Nature communications 11, 3542.
    11. Wang, W., Li, W., Ge, X., Yan, K., Mandava, C.S., Sanyal, S.#, and Gao, N.# (2020). Loss of a single methylation in 23S rRNA delays 50S assembly at multiple late stages and impairs translation initiation and elongation. PNAS 117, 15609-15619.
    12. Ye, Y., Wu, H., Chen, K., Clapier, C.R., Verma, N., Zhang, W., Deng, H., Cairns, B.R.#, Gao, N.#, and Chen, Z.# (2019). Structure of the RSC complex bound to the nucleosome. Science 366, 838-843.
    13. Zheng, L., Li, Y., Li, X., Zhong, Q., Li, N., Zhang, K., Zhang, Y., Chu, H., Ma, C., Li, G.#, Zhao, J.#, and Gao, N#. (2019). Structural and functional insights into the tetrameric photosystem I from heterocyst-forming cyanobacteria. Nat Plants 5, 1087-1097.
    14. Dong, D., Zheng, L., Lin, J., Zhang, B., Zhu, Y., Li, N., Xie, S., Wang, Y., Gao, N.#, and Huang, Z.# (2019). Structural basis of assembly of the human T cell receptor-CD3 complex. Nature 573, 546-552.
    15. Ma, C., Wu, X., Sun, D., Park, E., Catipovic, M.A., Rapoport, T.A.#, Gao, N.#, and Li, L.# (2019). Structure of the substrate-engaged SecA-SecY protein translocation machine. Nature communications 10, 2872.
    16. 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 177, 370-383 e315.
    17. 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 26, 258-266.
    18. 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.
    19. 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.
    20. 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.
    21. 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.
    22. 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.
    23. 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.
    24. 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.
    25. 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.
    26. 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.
    27. 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.
    28. 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.
    29. 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.
    30. 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.
    31. 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.
    32. 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.