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创新研究群体项目获得者

孙飞  博士 研究员 博士生导师  

国家“杰出青年基金”获得者
“长江学者奖励计划” 青年学者
2017第一届中国冷冻电镜杰出贡献奖
中国科学院生物物理研究所,生物大分子国家重点实验室,研究组长
中国科学院蛋白质科学研究平台生物成像中心首席科学家(兼主任)

研究方向:基于电子显微成像术的多尺度结构生物学研究与算法开发

电子邮件:feisun@ibp.ac.cn

电       话:010-64888442

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_xsszmQ_V/202005/t20200519_341385.html

课题组网站:http://www.ibp.cas.cn/feilab

蛋白质科学研究平台生物成像中心网站:http://ibp.cas.cn/cbi

简       历:

1997.08 - 2001.07   南京大学基础教学强化部,获理学学士学位

2001.08 - 2006.07   清华大学医学院,获生物物理学博士学位

2006.07 - 至今      中国科学院生物物理研究所,研究员;课题组组长;蛋白质科学研究平台生物成像中心首席科学家(兼主任)。

2015.09 - 至今      中国科学院大学生命科学学院 教授

获奖及荣誉:

2008  全国优秀博士论文奖;

2008  第八届"中央国家机关优秀青年";

2009  贝时璋青年生物物理学家奖;

2012  所带团队荣获中央国家机关"青年文明号"称号;

2017  中国生物物理学会冷电电子显微镜分会"杰出贡献奖";

2018  教育部"长江学者奖励计划"青年学者;

2020  国家杰出青年基金;

2021  北京市科学技术进步奖一等奖;

2022  中国科学院朱李月华优秀教师奖;

社会任职:

2018 - 至今 中国生物物理学会理事会常务理事

2018 - 至今 中国生物物理学会冷冻电子显微学分会理事会副理事长

2018 - 至今 北京电镜学会理事会副理事长

2018 - 至今 中国电子显微镜学会理事会常务理事

2014 - 至今 Biophysics Reports 副主编

2018 - 至今 International Union of Crystallography(IUCr)CryoEM分部编委

2021 - 至今 《生物物理与生物化学进展》副主编

2021 - 至今 《植物学报》编委

研究方向:

本研究组的主要研究兴趣是生物大分子复合体(如膜蛋白、超分子蛋白复合体)的结构与功能。我们的研究目标是综合多种结构生物学研究手段(以冷冻电镜技术和蛋白质晶体学技术为主)并发展新的结构研究技术方法,在多空间尺度上(从纳观到介观)、多时间尺度上(从静态到动态)、多层次上(体外和体内),来研究生物系统的高分辨率构造。我们以开展前沿科学研究为核心任务,同时注重培养高素质的人才。在未来的五年内,我们研究组的研究重点包括了四个方面:原位结构生物学技术和应用,超快冷冻电镜技术和应用,三维构造生物学技术和应用,膜蛋白的结构研究和定向改造。

1. 原位结构生物学技术和应用

经过30多年发展,尤其是近年的技术突破,冷冻电子显微术特别是单颗粒技术已成为结构生物学的主要手段之一。而蛋白质机器的原位结构解析是结构生物学的下一个突破点,特别是发展高分辨冷冻电子断层三维重构技术。然而,由于制样困难、原始数据完整度及信噪比低、图像解析复杂等,目前绝大部分蛋白质机器原位结构解析的分辨率还停留在20 埃左右。我们的研究兴趣是着重发展原位结构解析的完整技术平台,完善和优化原位结构解析流程中的冷冻离子减薄制样技术、倾转序列数据采集方法、电子断层三维重构新算法以及高通量高精度的蛋白质机器三维定位、对位和聚类分析算法。利用此技术平台,我们将解析一系列重要蛋白质复合体的原位高分辨率结构。

2. 超快冷冻电镜技术和应用

目前限制冷冻电镜分辨率提高的一个重要因素是生物样品的电子辐照损伤,而超快电镜技术为解决这个问题提供了新的机遇。超快电镜和冷冻电镜的成功结合将使我们可以实现蛋白质机器的低辐照损伤高分辨成像,同时能在多个时间尺度上研究蛋白质机器动态结构变化特征。这个领域在国际上尚未开展系统性的研究。我们的研究兴趣是着重发展生物超快冷冻电镜技术,一方面可以探索生物样品的脉冲电子辐照损伤深层次机制,尝试突破由于电子辐照损伤导致的信噪比瓶颈问题;另一方面对超级捕光复合物等重要蛋白质机器进行时间分辨率冷冻电镜成像,分析其时间分辨率的动态过程。

3. 三维构造生物学技术和应用

生物体组织和器官的三维超微结构对于人类认识自然和治疗疾病都有及其重要的意义。体电子显微学的突破性进展和样品制备技术进步,提高了样品的三维可视化细节,使细胞系统的超分辨率成像达到令人满意的程度。随着连续切片自动收集系统的出现和聚焦离子束扫描电镜的发展,连续切片技术日益成熟,自动化程度也大大提高。这些技术的发展拓展了体电子显微学在生物医学领域的应用。我们的研究兴趣是,联合生物成像中心的队伍建立和发展连续切片体电子显微成像技术、图像对位拼接技术和基于人工智能的图像自动识别分割处理等技术,并利用这一技术与相关单位合作,开展组织器官水平上的三维超微结构研究。

4. 膜蛋白的结构研究和定向改造

膜蛋白在人类和其他物种的生命活动中都起着至关重要的作用,如物质运输、能量转换和信号转导等。解析膜蛋白的三维结构对深入理解膜蛋白的生物学功能,并进行基于结构的分子定向改造,具有非常重要的意义。我们的研究兴趣是发展膜蛋白及其复合体的体外构建表达技术,并利用这些技术研究离子通道、G蛋白偶联受体等重要膜蛋白的结构与功能,在此基础上对膜蛋白进行设计改造,赋予它们新的功能,从而开启它们新的应用场景与应用方向。

承担项目情况:

代表论著:

ORCID: 0000-0002-0351-5144

完整论著https://www.ncbi.nlm.nih.gov/myncbi/1x1Uzxhrkpz5vj/bibliography/public/ 

代表性论著:

1)科学研究方面

1. Xu, J.#, Liao, C.#, Yin, C.C., Li, G.*, Zhu, Y.*, and Sun, F.* (2024). In situ structural insights into the excitation-contraction coupling mechanism of skeletal muscle. Sci Adv 10, eadl1126.

2. Zheng, L.#, Yang, T.#, Guo, H.#*, Qi, C.#, Lu, Y. #, Xiao, H., Gao, Y., Liu, Y., Yang, Y., Zhou, M., Nguyen, H., Zhu, Y.*, Sun, F.*, Zhang, C.*, Ji, X.* (2024). Cryo-EM structures of human SID-1 transmembrane family proteins and implications for their low-pH-dependent RNA transport activity. Cell Research 34, 80-83.

3. Wen, Z., Zhang, Y., Zhang, B., Hang, Y., Xu, L., Chen, Y., Xie, Q., Zhao, Q., Zhang, L., Li, G., Zhao, B., Sun, F.*, Zhai, Y.*, Zhu, Y.*, et al. (2023). Cryo-EM structure of the cytosolic AhR complex. Structure 31, 295-308 e294.

4. Tai, L.#, Yin, G.#, Huang, X., Sun, F.*, and Zhu, Y.* (2023). In-cell structural insight into the stability of sperm microtubule doublet. Cell Discov 9, 116.

5. Zhao, M.#, Zhu, Y.#, Zhang, L.#, Zhong, G.#, Tai, L., Liu, S., Yin, G., Lu, J., He, Q., Li, M., Zhao, R., Wang, H., Huang, W., Fan, C., Shuai, L., Wen, Z., Wang, C., He, X., Chen, Q., Liu, B., Xiong, X., Bu, Z.*, Wang, Y.*, Sun, F.*, Yang, J.* (2022). Novel cleavage sites identified in SARS-CoV-2 spike protein reveal mechanism for cathepsin L-facilitated viral infection and treatment strategies. Cell Discov 8, 53.

6. Zhai, C., Zhang, N., Li, X., Chen, X., Sun, F.*, and Dong, M.* (2022). Fusion and expansion of vitellogenin vesicles during Caenorhabditis elegans intestinal senescence. Aging Cell, e13719.

7. Tai, L.#, Zhu, Y.#, Ren, H.#, Huang, X., Zhang, C.*, and Sun, F.* (2022). 8 A structure of the outer rings of the Xenopus laevis nuclear pore complex obtained by cryo-EM and AI. Protein Cell 13, 760-777.

8. Zhu, G.#, Zeng, H.#*, Zhang, S.#, Juli, J., Tai, L., Zhang, D., Pang, X., Zhang, Y., Lam, S.M., Zhu, Y.*, Peng, G.*, Michel, H.*, Sun, F.* (2021). The Unusual Homodimer of a Heme-Copper Terminal Oxidase Allows Itself to Utilize Two Electron Donors. Angew Chem Int Ed Engl 60, 13323-13330.

9. Zhang, Y.#, Pang, X.#*, Li, J., Xu, J., Hsu, V.W.*, and Sun, F.* (2021). Structural insights into membrane remodeling by SNX1. Proc Natl Acad Sci U S A 118.

10. Xia, S.#, Lan, Q.#, Zhu, Y.#, Wang, C.#, Xu, W.#, Li, Y., Wang, L., Jiao, F., Zhou, J., Hua, C., Wang, Q., Cai, X., Wu, Y., Gao, J., Liu, H., Sun, G., Munch, J., Kirchhoff, F., Yuan, Z., Xie, Y., Sun, F.*, Jiang, S.*, Lu, L.* (2021). Structural and functional basis for pan-CoV fusion inhibitors against SARS-CoV-2 and its variants with preclinical evaluation. Signal Transduct Target Ther 6, 288.

11. Tai, L.#, Zhu, G.#, Yang, M.#, Cao, L., Xing, X., Yin, G., Chan, C., Qin, C., Rao, Z., Wang, X.*, Sun, F.*, Zhu, Y.* (2021). Nanometer-resolution in situ structure of the SARS-CoV-2 postfusion spike protein. Proc Natl Acad Sci U S A 118.

12. Du, J.#, Wang, D.#, Fan, H.#, Xu, C.#, Tai, L.#, Lin, S.#, Han, S., Tan, Q., Wang, X., Xu, T., Zhang, H., Chu, X., Yi, C., Liu, P., Wang, X., Zhou, Y., Pin, J., Rondard, P., Liu, H.*, Liu, J.*, Sun, F.*, Wu, B.*, Zhao, Q.* (2021). Structures of human mGlu2 and mGlu7 homo- and heterodimers. Nature 594, 589-593.

13. Zhu, G.#, Zeng, H.#, Zhang, S.#, Juli, J., Pang, X., Hoffmann, J., Zhang, Y., Morgner, N., Zhu, Y.*, Peng, G.*, Michel, H.*, Sun, F.* (2020). A 3.3 A-Resolution Structure of Hyperthermophilic Respiratory Complex III Reveals the Mechanism of Its Thermal Stability. Angew Chem Int Ed Engl 59, 343-351.

14. Zhang, D.#, Zhang, Y.#, Ma, J., Zhu, C., Niu, T., Chen, W., Pang, X., Zhai, Y., and Sun, F.* (2020). Cryo-EM structures of S-OPA1 reveal its interactions with membrane and changes upon nucleotide binding. Elife 9: e50294.

15. Shi, Y.#, Xin, Y.#, Wang, C.#, Blankenship, R.E., Sun, F.*, and Xu, X.* (2020). Cryo-EM structures of the air-oxidized and dithionite-reduced photosynthetic alternative complex III from Roseiflexus castenholzii. Sci Adv 6, eaba2739.

16. Qiao, A.#, Han, S.#, Li, X.#, Li, Z.#, Zhao, P.#, Dai, A., Chang, R., Tai, L., Tan, Q., Chu, X., Ma, L., Thorsen,T., Runge, S., Yang, D., Wang, M., Sexton, P., Wootten, D.*, Sun, F.*, Zhao, Q.*, Wu, B.* (2020). Structural basis of Gs and Gi recognition by the human glucagon receptor. Science 367, 1346-1352.

17. Lu J.#, Chan C.#, Yu L.#, Fan J.*, Sun F.* and Zhai Y.* (2020) Molecular mechanism of mitochondrial phosphatidate transfer by Ups1. Communications Biology, 3: 468.

18. Xia S.#, Liu M.#, Wang C.#, Xu W.#, Lan Q., Feng S., Qi F., Bao L., Du L., Liu S., Qin C., Sun F.&, Shi Z.&, Zhu Y.*&, Jiang S.*&, and Lu L.*& (2020) Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. Cell Research, 30 (4): 343-355. (&: co-senior authors)

19. Ren, Z.#, Zhang, Y.#, Zhang, Y., He, Y., Du, P., Wang, Z., Sun, F.*, and Ren, H.* (2019). Cryo-EM Structure of Actin Filaments from Zea mays Pollen. Plant Cell 31, 2855-2867.

20. Gong H.#, LI L.#, Xu A.#, Tang Y., Ji W., Gao R., Wang S., Yu L., Tian C., Li J., Yen H.Y., Lam S.M., Shui G., Yang X., Sun Y., Li X., Jia M., Yang C., Jiang B., Lou Z., Robinson C., Wong L.L., Guddat L.W., Sun F.*, Wang Q.* and Rao Z.* (2018), A electron transfer path connects subunits of a mycobacterial respiratory supercomplex. Science 362.

21. Xin Y.#, Shi Y.#, Niu T.#, Wang Q., Niu W., Huang X., Ding W., Yang L., Blankenship R. E., Xu X.* and Sun F.* (2018) Cryo-EM structure of the RC-LH core complex from an early branching photosynthetic prokaryote. Nature communications, 9:1568.

22. Lu G.#, Xu Y.#, Zhang K., Xiong Y., Li H., Cui L., Wang X., Lou J., Zhai Y.*, Sun F.* and Zhang X.C.* (2017), Crystal structure of E. coli apolipoprotein N-acyltransferase. Nature Communications, 8:15948.

23. Chen R.#, Gao B.#, Liu, X., Ruan F., Zhang Y., Lou J., Feng K., Wunsch C., Li S.M., Dai J.* and Sun F.* (2017), Molecular insights into the enzyme promiscuity of an aromatic prenyltransferase. Nat Chem Biol 13, 226-234.

24. Wei R.#, Wang X.#, Zhang Y., Mukherjee S., Zhang L., Chen Q., Huang X., Jing S., Liu C., Li S., Wang G., Xu Y., Zhu S., Williams A., Sun F.* and Yin C.C.* (2016), Structural insights into Ca2+ -activated long-range allosteric channel gating of RyR1. Cell Research 26: 977-994 (Cover story).

25. Zhou, Q.#, Li, J.#, Yu, H., Zhai, Y., Gao, Z., Liu, Y., Pang, X., Zhang, L., Schulten, K., Sun, F.*, Chen, C.* (2014). Molecular insights into the membrane-associated phosphatidylinositol 4-kinase IIalpha. Nature communications 5, 3552.

26. Pang, X., Fan, J., Zhang, Y., Zhang, K., Gao, B., Ma, J., Li, J., Deng, Y., Zhou, Q., Egelman, E.H., Hsu, V.W.*, Sun, F.* (2014). A PH domain in ACAP1 possesses key features of the BAR domain in promoting membrane curvature. Developmental cell 31, 73-86.

27. Wang, X.#, Xu, F.#, Liu, J.#, Gao, B., Liu, Y., Zhai, Y., Ma, J., Zhang, K., Baker, T.S., Schulten, K., Zheng, D.*, Pang, H.*, Sun, F.* (2013). Atomic model of rabbit hemorrhagic disease virus by cryo-electron microscopy and crystallography. PLoS Pathog 9, e1003132.

2)技术开发方面

1. Liu, G.#, Niu, T.#, Qiu, M., Zhu, Y., Sun, F.*, and Yang, G*. (2024). DeepETPicker: Fast and accurate 3D particle picking for cryo-electron tomography using weakly supervised deep learning. Nature communications 15, 2090.

2. Li, S.#, Wang, Z.#, Jia, X., Niu, T., Zhang, J., Yin, G., Zhang, X., Zhu, Y.*, Ji, G.*, and Sun, F.* (2023). ELI trifocal microscope: a precise system to prepare target cryo-lamellae for in situ cryo-ET study. Nat Methods 20, 276-283.

3. Li, S., Jia, X., Niu, T., Zhang, X., Qi, C., Xu, W., Deng, H., Sun, F.*, and Ji, G.* (2023). HOPE-SIM, a cryo-structured illumination fluorescence microscopy system for accurately targeted cryo-electron tomography. Commun Biol 6, 474.

4. Li, X.#, Lazic, I.# *, Huang, X.#, Wirix, M., Wang, L., Deng, Y., Niu, T., Wu, D., Yu, L., and Sun, F.* (2022). Imaging biological samples by integrated differential phase contrast (iDPC) STEM technique. J Struct Biol 214, 107837.

5. Zhang, J.#, Zhang, D.#, Sun, L.#, Ji, G., Huang, X., Niu, T., Xu, J., Ma, C., Zhu, Y., Gao, N., Xu, W., 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.

6. Huang, X.#, Zhang, L.#, Wen, Z., Chen, H., Li, S., Ji, G., Yin, C.C., and Sun, F.* (2021). Amorphous nickel titanium alloy film: A new choice for cryo electron microscopy sample preparation. Prog Biophys Mol Biol 160, 5-15.

7. Fan, H., Wang, B., Zhang, Y., Zhu, Y., Song, B., Xu, H., Zhai, Y., Qiao, M.*, and Sun, F.* (2021). A cryo-electron microscopy support film formed by 2D crystals of hydrophobin HFBI. Nature communications 12, 7257.

8. Zhai, Y.*, Zhang, D., Yu, L., Sun, F., and Sun, F.* (2019). SmartBac, a new baculovirus system for large protein complex production. J Struct Biol X 1, 100003.

9. Li X.#, Zhang S.#, Zhang J. and Sun F.* (2018), In situ protein micro-crystal fabrication by cryo-FIB for electron diffraction. Biophysics Reports, 4(6): 339-347. doi: 10.1007/s41048-018-0075-x.

10. Li S., Ji G.*, Shi Y., Klausen L.H., Niu T., Wang S., Huang X., Ding W., Zhang X., Dong M., Xu W., and Sun F.* (2018), High-vacuum optical platform for cryo-CLEM(HOPE): a new solution for non-integrated multiscale correlative light and electron microscopy. Journal of Structural Biology, 201(1): 63-75.

11. Wang, S., Li, S., Ji, G., Huang, X., and Sun, F.* (2017). Using integrated correlative cryo-light and electron microscopy to directly observe syntaphilin-immobilized neuronal mitochondria in situ. Biophys Rep 3, 8-16.

12. Shi, Y., Wang, L., Zhang, J., Zhai, Y., and Sun, F.* (2017). Determining the target protein localization in 3D using the combination of FIB-SEM and APEX2. Biophys Rep 3, 92-99.

13. Li, X.#, Ji, G.#*, Chen, X., Ding, W., Sun, L., Xu, W., Han, H., and Sun, F.* (2017). Large scale three-dimensional reconstruction of an entire Caenorhabditis elegans larva using AutoCUTS-SEM. J Struct Biol 200, 87-96.

14. Han, R.#, Wan, X.#, Wang, Z., Hao, Y., Zhang, J., Chen, Y., Gao, X., Liu, Z., Ren, F., Sun, F.*, Zhang, F.* (2017). AuTom: A novel automatic platform for electron tomography reconstruction. J Struct Biol 199, 196-208.

15. Zhang, J.#, Ji, G.#, Huang, X., Xu, W.*, and Sun, F.* (2016). An improved cryo-FIB method for fabrication of frozen hydrated lamella. J Struct Biol 194, 218-223.

16. Shan, H., Wang, Z., Zhang, F., Xiong, Y., Yin, C.C.*, and Sun, F.* (2016). A local-optimization refinement algorithm in single particle analysis for macromolecular complex with multiple rigid modules. Protein Cell 7, 46-62.

17. Deng, Y.#, Chen, Y.#, Zhang, Y., Wang, S., Zhang, F.*, and Sun, F.* (2016). ICON: 3D reconstruction with 'missing-information' restoration in biological electron tomography. J Struct Biol 195, 100-112.

18. Chen, Y.#, Zhang, Y.#, Zhang, K., Deng, Y., Wang, S., Zhang, F.*, and Sun, F.* (2016). FIRT: Filtered iterative reconstruction technique with information restoration. J Struct Biol 195, 49-61.

19. Han, R., Wang, L., Liu, Z., Sun, F.*, and Zhang, F.* (2015). A novel fully automatic scheme for fiducial marker-based alignment in electron tomography. J Struct Biol 192, 403-417.

授权专利:

1. 翟宇佳,孙飞,昆虫细胞-哺乳动物细胞表达穿梭载体 SmartBM-1 及其应用。发明专利,ZL202311601025.2。

2. 朱博玲,叶志楠,陈永圣,黄小俊,朱赟,孙飞,一种灭活冷冻电镜样品制备系统及制备方法。发明专利,202310952698.6。

3. 何佳,孙文浩,张艳,孙飞,杨戈,基于自监督深度学习的大尺度生物电镜各向同性超分辨三维重建技术。发明专利,ZL202211689462.X。

4. 刘国乐,牛彤欣,裘梦轩,孙飞,杨戈,朱赟,基于深度学习的冷冻电镜颗粒挑选方法、装置和电子设备。发明专利,ZL202211284170.8。

5. 季刚,黄小俊,孙飞,一种透射电镜分析用微阵列超薄支持膜的制备方法。发明专利,ZL201910843744.2。

6. 季刚,李喜霞,张建国,孙飞,一种适用于扫描/透射电子显微镜成像的自动聚焦方法。发明专利,ZL201910034869.0。

7. 范宏成,孙飞,乔明强,王波,朱赟,用疏水蛋白膜作为支持膜的电镜载网制备方法。发明专利,ZL202110576212.4。

8. 翟宇佳,孙飞,一种同时表达n个蛋白或蛋白亚基的方法及其专用系统。发明专利,ZL 201610248592.8。

9. 翟宇佳,孙飞,SmartBac杆状病毒表达系统及其应用。发明专利,ZL 201810028508.0。

10. 孙飞,庞效云,翟宇佳,王刚刚,谢天,用于在细菌表面呈递目的蛋白的DNA分子及其应用。发明专利,ZL201310750736.6。

11. 黄小俊,季刚,孙飞,透射电子显微镜载网制备方法。发明专利,ZL201510355339.8。

12. 季刚,李硕果,孙飞。一种光镜电镜关联成像用光学真空冷台。发明专利。ZL201410363314.8。

13. 季刚,王莉,徐伟,孙飞。摇床装置。发明专利。ZL201410550483.2。

装备设备研制:

1. 我国首台国产场发射透射电镜TH-F120,新华社广州1月20日电(记者马晓澄)。

2. 针对病理组织样本高通量成像需求的专用扫描透射电子显微镜SmartView研制成功,https://www.cas.cn/syky/202108/t20210809_4801432.shtml

3. 生物超快冷冻电子显微镜研制,http://www.ibp.cas.cn/zhxw/zxbd/202307/t20230714_6810057.html

(资料来源:孙飞研究员,2024-04-18)