张一小课题组致力于运用和发展冷冻电镜技术研究富有挑战性的生物学机制问题。其中重点关注细胞对机械力信号的感知和传导机制，创新性的发展了基于纳米磷脂盘和小脂质体的机械力环境模拟方法，首次实现了机械力环境下的电镜三维结构解析。通过对细菌、植物、哺乳动物中不同机械力通道的研究，系统性揭示了脂质及脂质化修饰在机械力感知过程中的重要作用。同时，课题组关注与神经退行疾病及细胞稳态维持相关的重大科学问题，通过结构生物学等手段阐释其分子机制并开发疾病干预手段。相关研究已在Nature (2024, 2021), Science (2023, 2020), Molecular Cell (2025, 2020a, 2020b), Science Advances (2025), Nature Communications (2025, 2024, 2021) 等国际期刊发表多篇高水平论文。近年来主持多个国家及地方基金及人才项目，并荣获中国科学院优秀导师，上海科技青年35under35，中国电子显微学会优秀青年学者奖，中国生物力学与力学生物学十大进展等奖项。

主要研究方向包括：

（1）与触觉、听觉等感知觉形成相关的机械力受体机制研究

（2）与神经退行疾病相关的生物大分子复合物结构与功能研究

（3）与细胞死亡、炎症、自噬相关的分子机制研究

SELECTED PUBLICATIONS:

1. Wang, X., Bai, Z., Wallis, C., Wang, H., Han, Y., Jin, R., Lei, M., Yang, T., Gu, C., Jessen, H., Shears, S.^#, Sun, Y.^#, Corry, B.^#, Zhang, Y.^# (2025). KIDINS220 and InsP8 safeguard the stepwise regulation of phosphate exporter XPR1. Molecular Cell, 17, 3209 - 3224

2. Han, Y., Han, Q., Tang, Q., Zhang, Y.^#, and Liu, K.^# (2025). Molecular basis for the stepwise and faithful maturation of the 20 S proteasome. Science Advances 11, eadr7943.

3. Han, Y., Zhou, Z., Jin, R., Dai, F., Ge, Y., Ju, X., Ma, X., He, S., Yuan, L., Wang, Y., Yang, W., Yue, X., Chen, Z., Sun, Y., Corry, B.^# , Cox, C. D.^#, and Zhang, Y.^# (2024). Mechanical activation opens a lipid-lined pore in OSCA ion channels. Nature, 1-9.

Highlithed with Nautre research briefing：Lipids act as structural components of the pore of an ion-channel family. Nature, 10.1038/d41586-024-02477-4

4. Zhang, Y., Dai, F., Chen, N., Zhou, D., Lee, C.-H.^#, Song, C.^#, Zhang, Y.^#, and Zhang, Z^#. (2024). Structural insights into VAChT neurotransmitter recognition and inhibition. Cell Research 34, 665-668. 10.1038/s41422-024-00986-5.

5. Zhou, Z., Ma, X., Lin, Y., Cheng, D., Bavi, N., Secker, G.A., Li, J.V., Janbandhu, V., Sutton, D.L., Scott, H.S., Zhang, Y. ^#, Cox, C.D.^# (2023). MyoD-family inhibitor proteins act as auxiliary subunits of Piezo channels. Science, 381, 799-804.

6. Yuan, L., Han, Y., Zhao, J., Zhang, Y.^#, and Sun, Y^#. (2023). Recognition and cleavage mechanism of intron-containing pre-tRNA by human TSEN endonuclease complex. Nature Communications, 14, 6071.

7. Xia, A., Wang, X., He, J., Wu, W., Jiang, W., Xue, S., Zhang, Q., Gao, Y., Han, Y., and Li, Y., Peng, X., Xie, M., Mayer, C. T., Liu, J., Hua, C., Sha, Y., Xu, W., Huang, J., Ying, T., Jiang, S., Xie, Y., Cai, Q., Lu, L. ^#, Silva, I. T. ^#, Yuan, Z. ^#, Zhang, Y.^#, and Wang, Q^#. (2023). Cross-reactive antibody response to Monkeypox virus surface proteins in a small proportion of individuals with and without Chinese smallpox vaccination history. BMC biology, 21, 205.

8. Zhang, Y., Daday, C., Gu, R., Cox, C.D., Martinac, B., Groot, B., Walz, T. (2021). Visualizing the mechanosensitive ion channel MscS under membrane tension. Nature, 590, 509-514.

9. Dan, J.*, Zhang, Y.*, Lee, C.H., Valencia-Sanchez, M., Zhang, J., Wang, M., Holder, M., Svetlov, V., Tan, D., Nudler, E., Reinberg, D., Walz, T., Armache, K. (2021). Structures of monomeric and dimeric PRC:EZH1 reveal flexible modules involved in chromatin compaction. Nature Communications, 12(1): 714.

10. Zhang, Y., Angiulli, G., Martinac, B., Cox, C. D., and Walz, T. (2021). Cyclodextrins for structural and functional studies of mechanosensitive channels. J Struct Biol X 5, 100053. 10.1016/j.yjsbx.2021.100053.

11. Sun, Y.*, Zhang, Y.*, Aik, W.S., Yang, X.-C., Marzluff, W.F., Walz, T., Dominski, Z., and Tong, L. (2020). Structure of an active human histone pre-mRNA 3’-end processing machinery. Science 367, 700-703.

12. Zhang, Y.*, Sun, Y.*, Shi, Y., Walz, T., and Tong, L. (2020). Structural Insights into the Human Pre-mRNA 3’-End Processing Machinery. Molecular Cell 77: 800-809.

13. Su, M.*, Zhu, L.*, Zhang, Y.*, Paknejad, N.*, Dey, R., Huang, J., Lee, M.Y., Williams, D., Jordan, K.D., Eng, E.T., Ernst, O.P., Meyerson, J., Hite, R., Walz, T., Liu, W., Huang, X. (2020). Structural basis of the activation of heterotrimeric Gs-protein by isoproterenol-bound b1-adrenergic receptor. Molecular Cell 80:59-71.

14. Nešić, D.*, Zhang, Y.*, Spasic, A.*, Li, J.*, Provasi, D., Filizola, M., Walz, T., and Coller, B.S. (2020). Cryo-Electron Microscopy Structure of the αIIbβ3-Abciximab Complex. Arteriosclerosis, Thrombosis, and Vascular Biology. 119.313671.

15. 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.

16. Lees, J.A.*, Zhang, Y.*, Oh, M.S., Schauder, C.M., Yu, X., Baskin, J.M., Dobbs, K., Notarangelo, L.D., De Camilli, P., Walz, T., Renisch, K. (2017). Architecture of the human PI4KIIIalpha lipid kinase complex. Proc Natl Acad Sci. U.S.A 114, 13720-13725.

17. Sun, Y.*, Zhang, Y.*, Hamilton, K., Manley, J.L., Shi, Y., Walz, T., and Tong, L. (2017). Molecular basis for the recognition of the human AAUAAA polyadenylation signal. Proc Natl Acad Sci. U.S.A 115, E1419-E1428.

18. 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. Nature Structural & Molecular Biology 21, 1042-1046.

19. Wu, S., Tutuncuoglu, B., Yan, K., Brown, H., Zhang, Y., Tan, D., Gamalinda, M., Yuan, Y., Li, Z., Jakovljevic, J., et al. (2016). Diverse roles of assembly factors revealed by structures of late nuclear pre-60S ribosomes. Nature 534, 133-137.

20. 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.

* indicates co-first authors, ^# indicates co-corresponding authors