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,6165cc金沙总站检测中心,北京大学
工作经历:
2017/4-至今,教授,6165cc金沙总站检测中心
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6165cc金沙总站检测中心
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
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。
1. Jiang, F., Shen, J., Cheng, J., Wang, X., Yang, J., Li, N., Gao, N., and Jin, Q. (2022). N-terminal signal peptides facilitate the engineering of PVC complex as a potent protein delivery system. Sci Adv 8, eabm2343.
2. Micic, J., Rodriguez-Galan, O., Babiano, R., Fitzgerald, F., Fernandez-Fernandez, J., Zhang, Y., Gao, N., Woolford, J.L., and de la Cruz, J. (2022). Ribosomal protein eL39 is important for maturation of the nascent polypeptide exit tunnel and proper protein folding during translation. Nucleic acids research.
3. 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.
4. Du, S., Wang, G., Zhang, Z., Ma, C., Gao, N.#, and Xiao, J.# (2022). Structural insights into how GlcNAc-1-phosphotransferase directs lysosomal protein transport. The Journal of biological chemistry 298, 101702.
5. Hu, X., Jiang, S., Xu, F., Zeng, C., Wang, X., Liu, W., Cheng, A., Ma, C., Gao, N., Zhao, Y., Dai, J., and Zhao, G. (2022). Engineering and functional analysis of yeast with a monotypic 40S ribosome subunit. PNAS 119, e2114445119.
6. 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.
7. Wang, X., Cheng, J., Shen, J., Liu, L., Li, N., Gao, N., Jiang, F., and Jin, Q. (2022). Characterization of Photorhabdus Virulence Cassette as a causative agent in the emerging pathogen Photorhabdus asymbiotica. Sci China Life Sci 65, 618-630.
8. Zhang, W.#, Li, Z., Sun, Y., Cui, P., Liang, J., Xing, Q., Wu, J., Xu, Y., Zhang, W., Zhang, Y.#, He, L.#, and Gao, N. (2022). Cryo-EM structure of Mycobacterium tuberculosis 50S ribosomal subunit bound with clarithromycin reveals dynamic and specific interactions with macrolides. Emerg Microbes Infect 11, 293-305.
9. Liu, Y., Ai, C., Gan, T., Wu, J., Jiang, Y., Liu, X., Lu, R., Gao, N., Li, Q., Ji, X., and Hu, J. (2021). Transcription shapes DNA replication initiation to preserve genome integrity. Genome Biol 22, 176.
10. 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.
11. Zhang, J., Zhang, D., Sun, L., Ji, G., Huang, X., Niu, T., Xu, J., Ma, C., Zhu, Y., Gao, N., Xu, W., and Sun, F. (2021). VHUT-cryo-FIB, a method to fabricate frozen hydrated lamellae from tissue specimens for in situ cryo-electron tomography. J Struct Biol 213, 107763.
12. 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.
13. Yang, H., Yu, Z., Chen, X., Li, J., Li, N., Cheng, J., Gao, N., Yuan, H.X., Ye, D., Guan, K.L., and Xu, Y. (2021). Structural insights into TSC complex assembly and GAP activity on Rheb. Nature communications 12, 339.
14. 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.
15. Du, S., Cao, Y., Zhu, Q., Yu, P., Qi, F., Wang, G., Du, X., Bao, L., Deng, W., Zhu, H., Liu, J., Nie, J., Zheng, Y., Liang, H., Liu, R., Gong, S., Xu, H., Yisimayi, A., Lv, Q., Wang, B., He, R., Han, Y., Zhao, W., Bai, Y., Qu, Y., Gao, X., Ji, C., Wang, Q., Gao, N., Huang, W., Wang, Y., Xie, X.S., Su, X.D., Xiao, J., and Qin, C. (2020). Structurally Resolved SARS-CoV-2 Antibody Shows High Efficacy in Severely Infected Hamsters and Provides a Potent Cocktail Pairing Strategy. Cell 183, 1013-1023 e13.
16. 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.
17. 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.
18. 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.
19. Cao, Y., Su, B., Guo, X., Sun, W., Deng, Y., Bao, L., Zhu, Q., Zhang, X., Zheng, Y., Geng, C., Chai, X., He, R., Li, X., Lv, Q., Zhu, H., Deng, W., Xu, Y., Wang, Y., Qiao, L., Tan, Y., Song, L., Wang, G., Du, X., Gao, N., Liu, J., Xiao, J., Su, X.D., Du, Z., Feng, Y., Qin, C., Qin, C., Jin, R., and Xie, X.S. (2020). Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients` B Cells. Cell 182, 73-84 e16.
20. 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.
21. Wang, Y., Wang, G., Li, Y., Zhu, Q., Shen, H., Gao, N., and Xiao, J. (2020). Structural insights into secretory immunoglobulin A and its interaction with a pneumococcal adhesin. Cell Res 30, 602-609.
22. Zhang, B., Jin, Q., Xu, L., Li, N., Meng, Y., Chang, S., Zheng, X., Wang, J., Chen, Y., Neculai, D., Gao, N., Zhang, X., Yang, F., Guo, J., and Ye, S. (2020). Cooperative transport mechanism of human monocarboxylate transporter 2. Nature communications 11, 2429.
23. Jin, Q., Zhang, B., Zheng, X., Li, N., Xu, L., Xie, Y., Song, F., Bhat, E.A., Chen, Y., Gao, N., Guo, J., Zhang, X., and Ye, S. (2020). Cryo-EM structures of human pannexin 1 channel. Cell Res 30, 449-451.
24. Li, Y., Wang, G., Li, N., Wang, Y., Zhu, Q., Chu, H., Wu, W., Tan, Y., Yu, F., Su, X.D., Gao, N., and Xiao, J. (2020). Structural insights into immunoglobulin M. Science 367, 1014-1017.
25. 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.
26. 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.
27. 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.
28. 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.
29. Zhu, X., Zhang, W., Guo, J., Zhang, X., Li, L., Wang, T., Yan, J., Zhang, F., Hou, B., Gao, N., Gao, G.F., and Zhou, X. (2019). Noc4L-Mediated Ribosome Biogenesis Controls Activation of Regulatory and Conventional T Cells. Cell Rep 27, 1205-1220 e1204.
30. Dong, L., Guan, X., Li, N., Zhang, F., Zhu, Y., Ren, K., Yu, L., Zhou, F., Han, Z., Gao, N., and Huang, Z. (2019). An anti-CRISPR protein disables type V Cas12a by acetylation. Nat Struct Mol Biol 26, 308-314.
31. Wang, J., Wang, J., Hu, M., Wu, S., Qi, J., Wang, G., Han, Z., Qi, Y., Gao, N., Wang, H.W., Zhou, J.M., and Chai, J. (2019). Ligand-triggered allosteric ADP release primes a plant NLR complex. Science 364, eaav5868.
32. 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.
33. 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.
34. 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.
35. 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 115, 7039-7044.
36. 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.
37. 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.
38. 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.
39. 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.
40. 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.
41. 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.
42. 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.
43. 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.
44. 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 14, 1306-1313
45. 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.
46. 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.
47. 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.
48. 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.
49. 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.
50. 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.
51. 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.
52. 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.
53. 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.
54. Du, W., Su, Q.P., Chen, Y., Zhu, Y., Jiang, D., Rong, Y., Zhang, S., Zhang, Y., Ren, H., Zhang, C., Wang, X., Gao, N., Wang, Y., Sun, L., Sun, Y., and Yu, L. (2016). Kinesin 1 Drives Autolysosome Tubulation. Developmental cell 37, 326-336.
55. 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.
56. Ding, Y.H., Fan, S.B., Li, S., Feng, B.Y., Gao, N., Ye, K., He, S.M., and Dong, M.Q. (2016). Increasing the Depth of Mass-Spectrometry-Based Structural Analysis of Protein Complexes through the Use of Multiple Cross-Linkers. Analytical chemistry 88, 4461-4469.
57. Tan, D., Li, Q., Zhang, M.-J., Liu, C., Ma, C., Zhang, P., Ding, Y.-H., Fan, S.-B., Tao, L., Yang, B., Li, X., Ma, S., Liu, J., Feng, B., Liu, X., Wang, H.-W., He, S.-M., Gao, N., Ye, K., Dong, M.-Q., and Lei, X. (2016). Trifunctional cross-linker for mapping protein-protein interaction networks and comparing protein conformational states. eLife 5, e12509.
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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。