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生物大分子国家重点实验室

朱平博士研究员博士生导师

国家“杰出青年科学基金”获得者　　 中科院生物物理所，生物大分子国家重点实验室，研究组长

研究方向：冷冻电子显微学；染色质结构与表观遗传调控；病毒感染与复制机制

电子邮件：zhup@ibp.ac.cn

电话：010-64888799 (office), 010-64888813 (lab)

通讯地址：北京市朝阳区大屯路15号（100101）

英文版个人网页：http://english.ibp.cas.cn/en_sourcedb_ibp/rck/EN_xsszmZ/202005/t20200519_341353.html

简历：

　　1986.09 - 1990.06 浙江大学学士

　　1990.09 - 1993.06 西安交通大学硕士

　　1993.09 - 1997.06 清华大学博士

　　1997.07 - 1998.12 清华大学讲师

　　1999.03 - 2008.05 美国佛罗里达州立大学生物系博士后、助理研究员、副研究员（Non tenure-track faculty系列）

　　2008.06 - 至今中国科学院生物物理研究所课题组长

　　2014 获国家“杰出青年科学基金”资助

获奖及荣誉：

社会任职：

研究方向：

　　本课题组研究工作主要包括以下方向：（1）冷冻电子显微学；（2）染色质结构与表观遗传调控；（3）病毒感染与复制机制。欢迎有兴趣的同学报考本研究组，招生相关信息请参阅中国科学院大学相关网页，也欢迎其他感兴趣的成员加入本组。

1. 冷冻电子显微学

　　冷冻电镜三维重构技术可以解析天然状态下生物大分子及其复合物的空间结构及组装机制，为深入理解生物大分子的相互作用机理提供重要而有益的信息。本课题组以冷冻电镜（Cryo-EM)和电子断层成像（Electron Tomography）技术为主要手段进行重要生物大分子及复合物的结构和功能研究、细胞内分子机器的原位结构解析，以及重要生命过程的可视化研究。同时，我们也针对冷冻电镜三维重构中涉及到的步骤和流程开展方法学研究。

2. 染色质结构与表观遗传调控

　　染色质的结构和动态变化对于不同功能的各种细胞的命运决定和分化起着关键性的作用。染色质高级结构与功能调控是生命延续中最为基础的根本问题之一，对于理解生命过程的本质具有十分重要的意义。在前期研究中，我们利用冷冻电镜技术解析了由12个核小体通过连接组蛋白H1形成的30nm染色质纤维的分辨率为11Å的三维结构，揭示了30nm染色质纤维的左手双螺旋高级结构模型，在染色质的高级结构组装及调控这一生命科学的基本问题上取得了重要进展（Science2014，Research Article）。目前，我们正致力于获得30nm染色质的原子分辨率精细结构，以及各种表观遗传调控因子，如不同的组蛋白变体和修饰、不同的染色质构造及重塑因子、以及不同的连接DNA长度和连接组蛋白等，对核小体、染色质的组装，以及染色质高级结构形成和维持的分子调控机制。

3. 病毒感染与复制机制

　　病毒是一个高效组装的分子机器，对其精细结构的解析对于理解病毒分子的组装、感染、复制及调控机制都有重要意义。利用冷冻电镜三维重构技术，我们对双链RNA以及其它种类病毒在病毒生命周期中不同状态的全病毒结构，以及病毒的组装、感染、转录、复制及其分子调控等方面进行了较为系统的研究。今后，我们将继续进行不同宿主、具有不同感染和致病性的病毒在其生命周期中不同状态下的高分辨率结构解析，从而研究病毒生命周期不同阶段的分子调控机制，以及病毒的感染及复制机制。同时，我们也在进行重要病原体的疫苗结构学评价研究。

承担项目情况：

代表论著：

1. Li J^#, Zhang HN^#, Li D, Liu YJ, Bayer EA, Cui Q, Feng Y*,Zhu P*. (2023) Structure of the transcription open complex of distinct σ^Ifactors.Nat. Comm., 14: 6455 (*corresponding author)

2. Li Y^#, Zhang HN^#, Li X^#, Wu W,Zhu P*. (2023) Cryo-ET study from in vitro to in vivo revealed a general folding mode of chromatin with two-start helical architecture.Cell Rep., 42:113134 (*corresponding author)

3. Huang L^#, Wang Y^#, Long H^#*, Zhu H, Wen Z, Zhang L, Zhang W, Guo Z, Wang L, Tang F, Hu J, Bao K,Zhu P*, Li G*, Zhou Z*. (2023) Structural insight into H4K20 methylation on H2A.Z-nucleosome by SUV420H1.Mol. Cell, 83(16):2884-95 (*corresponding author, cover)

4. Zhang HN^#, Li Y^#, Liu Y, Li D, Wang L, Song K, Bao K,Zhu P*. (2023) A method for restoring signals and revealing individual macromolecule states in cryo-ET, REST.Nat. Comm.,14:2937 (* corresponding author)

5. Zhang H^#, Li H^#, Zhang F*,Zhu P*. (2023) A strategy combining denoising and cryo-EM single particle analysis. Brief. Bioinform., 24(3):bbad148 (* corresponding author)

6. Bao K^#, Zhang X^#, Li D^#, Sun W, Sun Z, Wang J*,Zhu P*. (2022) In situ structures of polymerase complex of mammalian reovirus illuminate RdRp activation and transcription regulation.Proc. Natl. Acad. Sci. USA, 119(50):e2203054119 (* corresponding author)

7. Li D^#, Zhang X^#, Wang Y^#, Zhang H, Song K, Bao K,Zhu P*. (2022) A new polymorphism of human amylin fibrils with similar protofilaments and a conserved core.iScience, 25(12):105705 (* corresponding author)

8. Huang X^#, Wang Y^#, Yu C^#, Zhang H^#, Ru Q^#, Li X, Song K, Zhou M,Zhu P*. (2022) Cryo-EM structures reveal the dynamic transformation of human alpha-2-macroglobulin working as a protease inhibitor.SCI. CHINA Life Sci., 65(12):2491–2504 (*corresponding author)

9. Li H^#, Zhang H^#, Wan X, Yang Z, Li C, Li J, Han R*,Zhu P*, Zhang F*. (2022) Noise-Transfer2Clean: Denoising cryo-EM images based on noise modeling and transfer.Bioinformatics, 38(7), 2022–29 (*corresponding author)

10. Bao K^#, Qi X^#, Li Y, Gong M, Wang X*,Zhu P*. (2022) Cryo-EM structures of infectious bursal disease virus with different virulence provide insights on their assembly and invasion.Science Bull., 67(6):646-54 (*corresponding author)

11. Zhu X, Zhang X*,Zhu P*. (2022) Study on the influences of different metal ions on the formation of human islet amyloid polypeptide fibrils.J. Chin. Elec. Micro. Soc., 41(3):265-71 (*corresponding author, in Chinese)

12. Zhou M^#, Dai L^#, Li C, Shi L, Huang Y, Guo Z, Wu F,Zhu P*, Zhou Z*. (2021) Structural mechanism of nucleosome dynamics governed by human histone variants H2A.B and H2A.Z.2.2.EMBO J., 40(1):e105907 (*corresponding author)

13. Zhang X, Li D, Zhu X, Wang Y,Zhu P*. (2020) Structural characterization and cryo-electron tomography analysis of human islet amyloid polypeptide suggest a synchronous process of the hIAPP_1-37amyloid fibrillation.Biochem. Biophys. Res. Comm., 533(1):125-131(*corresponding author)

14. Guan H^#, Wang Y^#, Perculija V, Saeed AF, Liu Y, Li J, Jan SS, Li Y,Zhu P*, Ouyang S*. (2020) Cryo-electron microscopy structure of the SADS-CoV spike glycoprotein provides insights into an evolution of unique coronavirus spike proteins.J. Virol., 94(22):e01301-20. (*corresponding author)

15. Yang W^#, Wang Y^#, Guo J^#, He L, Zhou Y, Zheng H, Liu Z,Zhu P*, Zhang XC*. (2020) Cryo‐electron microscopy structure of CLHM1 ion channel from Caenorhabditis elegans.Protein Sci., 29(8):1803-15 (*corresponding author)

16. Guan H^#, Wang Y^#, Yu T^#, Huang Y^#, Li M, Saeed AF, Perculija V, Li D, Xiao J, Wang D,Zhu P*, Ouyang S*. (2020) Cryo-EM structures of the human PA200 and PA200-20S complex reveal regulation of proteasome gate opening and two PA200 apertures.PLoS Biol., 18(3): e3000654 (*corresponding author)

17. Cao J^#, Zhang J^#, Lu Y, Luo S*, Zhang J*,Zhu P*. (2019) Cryo-EM structure of native spherical subviral particles isolated from HBV carriers.Virus Res., 259:90-96 (*corresponding author)

18. Wang H^#, Guo Z^#, Feng H, Chen Y, Chen X, Li Z, Hernández-Ascencio W, Dai X, Zhang Z, Zheng X, Mora-López M, FU Y, Zhang C,Zhu P*, Huang L*. (2018) Novel Sulfolobus virus with an exceptional capsid architecture.J. Virol., 92(5): e01727-17 (*corresponding author)

19. Zhu P*, Li G*. (2016) Higher-order structure of the 30-nm chromatin fiber revealed by cryo-EM.IUBMB Life. 68(11):873-78 (*corresponding author,invited review, cover)

20. Xu P^#, Li C^#, Chen Z, Jiang S, Fan S, Wang J, Dai J,Zhu P*, Chen Z*. (2016) The NuA4 core complex acetylates nucleosomal histone H4 through a double recognition mechanism,Mol. Cell, 63(6):965–75 (*corresponding author)

21. Zhu P*, Li G*. (2016) Structural insights of nucleosome and the 30-nm chromatin fiber.Curr. Opin.Struc. Biol., 36:106-15 (*corresponding author,invited review)

22. Zhu HT,Zhu P*. (2015) No longer ‘blob-ology’: Cryo-EM is getting into molecular details.SCI. China Life Sci, 58(11): 1154-6 (*corresponding author,insight)

23. Li C^#, Zhou M^#, Li X,Zhu P*. (2015) Application of cryo-electron microscopy on epigenetic studies.Prog. in Biochem. & Biophys., 42(11):1063-72 (*corresponding author, in Chinese,invited review)

24. Li X^#, Feng H^#, Zhang J, Sun L,Zhu P*. (2015) Analysis of Chromatin Fiber in Hela Cell with Electron Tomography.Biophys. Report, 1(1): 51-60 (*corresponding author,cover story)

25. Li Z, Qi X, Ren X, Cui L, Wang X*,Zhu P*. (2015) Molecular characteristics and evolutionary analysis of a very virulent infectious bursal disease virus.SCI. China Life Sci., 58(8): 731-38 (*corresponding author,cover story)

26. Li G*,Zhu P*. (2015) Structure and organization of chromatin fiber in the nucleus.FEBS Lett., 589(20):2893-2904 (*corresponding author,invited review)

27. Yao Q, Lu Q, Wan X, Song F, Xu Y, Hu M, Zamyatina A, Liu X, Huang N,Zhu P*, Shao F*. (2014) A structural mechanism for bacterial autotransporter glycosylation by a dodecameric heptosyltransferase family.elife, 3:e03714 (*corresponding author)

28. Gong M^#, Zhu H^#, Zhou J, Yang C, Feng J, Huang X, Ji G, Xu H*,Zhu P*. (2014) Cryo-EM study of insect cell-expressed Enterovirus 71 and Coxsackievirus A16 virus-like particles provides a structural basis for vaccine development.J. Virol., 88(11):6444-52 (*corresponding author)

29. Chen P,Zhu P*, Li G*. (2014) New insights into the helical structure of 30-nm chromatin fibers.Protein & Cell, 5(7):489-91 (*corresponding author)

30. Song F^#, Chen P^#, Sun D, Wang M, Dong L, Liang D, Xu RM,Zhu P*, Li G*. (2014) Cryo-EM study of the chromatin fiber reveals a double helix twisted by tetranucleosomal units.Science, 344 (6182): 376-80 (*corresponding author,Research Article)

31. Cheng L^#, Huang X^#, Li X, Xiong W, Sun W, Yang C, Zhang K, Wang Y, Liu H, Huang X, Ji G, Sun F, Zheng C*,Zhu P*. (2014) Cryo-EM structures of two bovine adenovirus type 3 intermediates.Virology, 450-451:174-81 (*corresponding author)

32. Zhu H^#, Zhuang J^#, Feng H, Liang R, Wang J, Xie L*,Zhu P*. (2014) Cryo-EM structure of isomeric molluscan hemocyanin triggered by viral infection.PLoS One, 9(6): e98766 (*corresponding author)

33. Liu J, Zhu H, Feng H, Gong M,Zhu P*. (2014) Architecture of Human HDAC1/2-RbAp46/48 Core Protein Complex Revealed by Electron Microscopy.Prog. in Biochem. & Biophys., 2014, 41(6): 591-97 (*corresponding author, in Chinese)

34. Sun D, Song F, Huang L, Zhang K, Ji G, Chen P*,Zhu P*. (2013) In vitro Assembly and Electron Microscopic Analysis of 30 nm Chromatin Fibers.Prog. in Biochem. & Biophys., 2013, 40(7): 739-47 (*corresponding author, in Chinese,cover story)

35. Yang C, Ji G, Liu H, Zhang K, Liu G, Sun F,Zhu P*, Cheng L*. (2012) Cryo-EM Structure of a transcribing cypovirus.Proc. Natl. Acad. Sci. USA, 109(16):6118-23 (*corresponding author)

36. Cheng L^#, Sun J^#, Zhang K, Mou Z, Huang X, Ji G, Sun F, Zhang J*,Zhu P*. (2011) Atomic model of a cypovirus built from cryo-EM structure provides insight into the mechanism of mRNA capping.Proc. Natl. Acad. Sci. USA, 108(4):1373–78 (* corresponding author)

37. Huang X, Song X,Zhu P*. (2010) Cryo Electron Tomography and Its Application to Biological Research.Acta Biophysica Sinica, 26 (7): 570-578 (*corresponding author, invited review, in Chinese)

38. Zhu P, Winkler H, Chertova E, Taylor K, Roux K*. (2008) Cryoelectron tomography of HIV-1 envelope spikes: further evidence for tripod-like legs.PLoS Pathog, 4(11): e1000203.

39. Zhu P, Liu J, Bess J., Chertova E, Lifson J, Grisé H, Ofek G, Taylor K, Roux K*. (2006) Distribution and Three-Dimensional Structure of AIDS Virus Envelope Spikes.Nature, 441:847-852 (Article)

40. Zhu P, Chertova E., Bess J, Lifson J, Arthur L, Liu J, Taylor KA, Roux KH*. (2003) Electron tomography analysis of envelope glycoprotein trimers on HIV and simian immunodeficiency virus virions.Proc. Natl. Acad. Sci. USA, 100(26):15812-15817

41. Zhu P, Olson WC, Roux KH*. (2001) Structural Flexibility and Function Valency of CD4-IgG2 (PRO 542): Potential for Crosslinking HIV-1 Envelope Spikes,J Virol., 75(14):6682-6686.

（资料来源：朱平研究员，2023-10-16）