1997.08 - 2001.07 Nanjing University, China, B.Sc. in Biophysics

2001.08 - 2006.07 Tsinghua University, China, Ph.D. in Biophysics

2006.07 - present Principal Investigator, Institute of Biophysics, Chinese Academy of Sciences; Chief scientist and director, Center for Biological Imaging, Core Facilities for Protein Sciences, Chinese Academy of Sciences, Beijing, China.

2015.09 - present Professor, School of Life Science, University of Chinese Academy of Sciences

Zhu Li Yuehua Outstanding Teacher Award, CAS, 2022

First Prize of Beijing Science and Technology Progress Award, 2021

China National Funds for Distinguished Young Scientists, 2020

National Middle-&-Youth Talent of Science and Technology Innovation, 2019

Youth professor, Chang Jiang Scholars Program of China, 2018

Outstanding contribution of Chinese cryo-electron microscopy society, 2017

National Youth Top-notch Talent, 2012

Beishi Zhang Prize for Young Scientist in Biophysics, 2009

Top 100, Excellent Ph.D thesis of China, 2008

Our research interests are mainly related with the structure and function of biological system from molecular level to cellular level. The aim of our group is to combine various structural approaches as well as developing new methodologies to determine the architecture of biological system, in vitro and in vivo, from nano-scale to meso-scale, from static to dynamic. Our core task is conducting cutting-edge scientific research, and fostering high-quality talents. In the next five years, we will focus on (i) in situ structural biology, (ii) Ultrafast cryo-EM technology and applications, (iii) 3D architectural biology, (iv) Structural studies of membrane proteins and structure-guided protein design.

1. In situ structural biology

After more than 30 years of development and especially the recent technological breakthroughs, cryo-electron microscopy technology (cryo-EM), such as single particle analysis, has become one of the major tools to study structures of macromolecular complexes, opening a new era of structural biology. In the future, the structural study of macromolecular complexes in their intact cellular environment will become the next breakthrough of structural biology, which will be achieved with the further development of cryo-EM technology. However, due to the difficulty of sample preparation, low data integrity and low signal-to-noise ratio, most in situ structures of protein complexes only have resolutions worse than 20 angstroms. Our research interest is to focused on the development of a complete technology platform for in situ structural biology, improving and optimizing the current techniques, which include cryo-focused ion beam technique, new data collection method and strategy, and new algorithm in image processing and data mining. Using these technology platform, we will study the in situ structures of a series of important macromolecular complexes in high resolution and unravel their functions.

2. Ultrafast cryo-EM technology and applications

The electron irradiation damage is a major factor to limit the resolution of biological samples in cryo-EM technology. The emerging ultrafast electron microscopy (UEM) provides a new opportunity to solve this problem. The successful combination of UEM and cryo-EM will enable us to yield a new technique cryo-UEM and achieve high resolution imaging without radiation damage. In addition, the pump-probe mode of UEM provides us a unique tool to study the time resolved structural dynamics of macromolecular complexes from pico-second to nano-second. One way of this technique is to perform cryo-UEM in diffraction mode, which is called cryo-UED. Our research interests are focused on developing cryo-UEM and cryo-UED techniques, then exploring the physical mechanism of electron irradiation damage, and studying several important protein complexes to analyze their time-resolved dynamic process.

3. 3D architectural biology techniques and appilcations

The three-dimensional ultrastructures of biological tissues and organs are of great significance to understand nature and treat human diseases. Recent technology advances of volume electron microscopy (VEM) along with serial sectioning techniques as well as the fast development of big data technology have allowed us to study the architectures of tissues and organs in 3D space and nano-meter resolution, which is called 3D architectural biology. With our recent developed VEM technique (AutoCUTS-SEM) and more in next step in collaborating with Center for Biological Imaging, Institute of Biophysics, we will focus on image processing algorithm developments including registration, segmentation, annotation and quantification, then studying three dimensional ultrastructures of important tissue model systems and investigating quantitative relations between 3D architectures and diseases.

4. Structural studies of membrane proteins and structure-guided protein design

Membrane proteins play a vital role in the life activities of humans and other species, such as material transport, energy conversion and signal transduction. Resolving and analyzing the three-dimensional structure of membrane proteins is of great significance for in-depth understanding of the biological functions of membrane proteins and for conducting structure-guided protein design. The aim of our research is to develop in vitro construction and expression technologies for membrane proteins and their complexes, and to use these technologies to study the structure and function of important membrane proteins, such as ion channels and G protein-coupled receptors, and to design and modify membrane proteins to give them new functions, thus opening up new application scenarios and directions.

ORCID: 0000-0002-0351-5144

Full list of publications:

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

Representative Publications:

1）Scientific research

1. Xu, J.^#, Liao, C.^#, Yin, C.C., Li, G.*, Zhu, Y.*, andSun, F.*(2024). In situ structural insights into the excitation-contraction coupling mechanism of skeletal muscle.Sci Adv10, 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 Research34, 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.Structure31, 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 Discov9, 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 Discov8, 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.*, andSun, F.*(2022). 8 A structure of the outer rings of the Xenopus laevis nuclear pore complex obtained by cryo-EM and AI.Protein Cell13, 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 Engl60, 13323-13330.

9. Zhang, Y.^#, Pang, X.^#*, Li, J., Xu, J., Hsu, V.W.*, andSun, F.*(2021). Structural insights into membrane remodeling by SNX1.Proc Natl Acad Sci U S A118.

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 Ther6, 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 A118.

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.Nature594, 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 Engl59, 343-351.

14. Zhang, D.^#, Zhang, Y.^#, Ma, J., Zhu, C., Niu, T., Chen, W., Pang, X., Zhai, Y., andSun, F.*(2020). Cryo-EM structures of S-OPA1 reveal its interactions with membrane and changes upon nucleotide binding.Elife9: 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 Adv6, 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.Science367, 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 Cell31, 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.Science362.

21. Xin Y.^#, Shi Y.^#, Niu T.^#, Wang Q., Niu W., Huang X., Ding W., Yang L., Blankenship R. E., Xu X.* andSun 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.* andSun F.*(2017), Molecular insights into the enzyme promiscuity of an aromatic prenyltransferase.Nat Chem Biol13, 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 Research26: 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 communications5, 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 cell31, 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 Pathog9, e1003132.

2）Technology development

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 communications15, 2090.

2. Li, S.^#, Wang, Z.^#, Jia, X., Niu, T., Zhang, J., Yin, G., Zhang, X., Zhu, Y.*, Ji, G.*, andSun, F.*(2023). ELI trifocal microscope: a precise system to prepare target cryo-lamellae for in situ cryo-ET study.Nat Methods20, 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 Biol6, 474.

4. Li, X.^#, Lazic, I.^#*, Huang, X.^#, Wirix, M., Wang, L., Deng, Y., Niu, T., Wu, D., Yu, L., andSun, F.*(2022). Imaging biological samples by integrated differential phase contrast (iDPC) STEM technique.J Struct Biol214, 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 Biol213, 107763.

6. Huang, X.^#, Zhang, L.^#, Wen, Z., Chen, H., Li, S., Ji, G., Yin, C.C., andSun, F.*(2021). Amorphous nickel titanium alloy film: A new choice for cryo electron microscopy sample preparation.Prog Biophys Mol Biol160, 5-15.

7. Fan, H., Wang, B., Zhang, Y., Zhu, Y., Song, B., Xu, H., Zhai, Y., Qiao, M.*, andSun, F.*(2021). A cryo-electron microscopy support film formed by 2D crystals of hydrophobin HFBI.Nature communications12, 7257.

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

9. Li X.^#, Zhang S.^#, Zhang J. andSun 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., andSun 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., andSun, F.*(2017). Using integrated correlative cryo-light and electron microscopy to directly observe syntaphilin-immobilized neuronal mitochondria in situ.Biophys Rep3, 8-16.

12. Shi, Y., Wang, L., Zhang, J., Zhai, Y., andSun, F.*(2017). Determining the target protein localization in 3D using the combination of FIB-SEM and APEX2.Biophys Rep3, 92-99.

13. Li, X.^#, Ji, G.^#*, Chen, X., Ding, W., Sun, L., Xu, W., Han, H., andSun, F.*(2017). Large scale three-dimensional reconstruction of an entire Caenorhabditis elegans larva using AutoCUTS-SEM.J Struct Biol200, 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 Biol199, 196-208.

15. Zhang, J.^#, Ji, G.^#, Huang, X., Xu, W.*, andSun, F.*(2016). An improved cryo-FIB method for fabrication of frozen hydrated lamella.J Struct Biol194, 218-223.

16. Shan, H., Wang, Z., Zhang, F., Xiong, Y., Yin, C.C.*, andSun, F.*(2016). A local-optimization refinement algorithm in single particle analysis for macromolecular complex with multiple rigid modules.Protein Cell7, 46-62.

17. Deng, Y.^#, Chen, Y.^#, Zhang, Y., Wang, S., Zhang, F.*, andSun, F.*(2016). ICON: 3D reconstruction with 'missing-information' restoration in biological electron tomography.J Struct Biol195, 100-112.

18. Chen, Y.^#, Zhang, Y.^#, Zhang, K., Deng, Y., Wang, S., Zhang, F.*, andSun, F.*(2016). FIRT: Filtered iterative reconstruction technique with information restoration.J Struct Biol195, 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 Biol192, 403-417.

• Authorized Patents

1. Zhai Yujia;Sun Fei. SmartBM-1, an expression shuttle vector in insect cell-mammalian cell and its application. ZL202311601025.2.

2. Zhu Boling; Ye Zhinan; Chen Yongsheng; Huang Xiaojun; Zhu Yun;Sun Fei. A preparation system and preparation method for inactivated Cryo-EM Samples. 20231095P2698.6.

3. He Jia; Sun Wenhao; Zhang Yan;Sun Fei; Yang Ge. Isotropic reconstruction of large-scale biological electron microscopy based on self-supervised deep learning technique. ZL202211689462.X.

4. Liu Guole; Niu Tongxin; Qiu Mengxuan;Sun Fei; Yang Ge; Zhu Yun. Particle picking methods, devices and electronic equipment for cryo-electron microscopy based on deep learning. ZL202211284170.8.

5. Ji Gang; Huang Xiaojun;Sun Fei. A preparation method of ultra-thin microarray support film for transmission electron microscopy. ZL201910843744.2.

6. Ji Gang; Li Xixia, Zhang Jianguo,Sun Fei. An automatic focusing method for scanning/ transmission electron microscopy imaging. ZL201910034869.0.

7. Fan Hongcheng;Sun Fei; Qiao Mingqiang; Wang Bo; Zhu Yun. A preparation method of electron microscope grid using hydrophobin membrane as supporting membrane. ZL202110576212.4.

8. Zhai Yujia;Sun Fei. A method and special system for expressing n proteins or protein subunits simultaneously. ZL 201610248592.8.

9. Zhai Yujia;Sun Fei. SmartBac Baculovirus Expression System and Its Application. ZL 201810028508.0.

10.Sun Fei; Pang Xiaoyun; Zhai Yujia; Wang Ganggang; Xie Tian. DNA molecule for presenting target protein on bacteria surface and its application. ZL201310750736.6.

11. Huang Xiaojun; Ji Gang;Sun Fei. Preparation method of grid of transmission electron microscope. ZL201510355339.8.

12. Ji Gang; Li Shuoguo;Sun Fei. An optical vacuum cooling stage for correlation imaging of light and electron microscopy. ZL201410363314.8.

13. Ji Gang; Wang Li; Xu Wei;Sun Fei. Shaking device. ZL201410550483.2.

• Instrument development

1. China's first self-developed commercial field emission transmission electron microscope was releasedhttp://www.eguangzhou.gov.cn/2024-01/24/c_958962.htm.

2. Successfully developed SmartView dedicated scanning transmission electron microscope for high-throughput imaging of pathological tissue sampleshttps://www.cas.cn/syky/202108/t20210809_4801432.shtml.

3. Development of biological ultrafast cryo-electron microscope,//www.wyreworks.com/zhxw/zxbd/202307/t20230714_6810057.html.

(From Fei Sun, April 18, 2024)