• 中央高校优秀青年教师科研创新基金（2023―2024），主持
• 细胞活动与逆境适应教育部重点实验室开放课题基金（2023），主持
• 甘肃省杰出青年项目（2023―2026），主持
• 甘肃省创新群体项目（2023―2026），参与
• 细胞活动与逆境适应教育部重点实验室开放课题基金（2021），主持
• 中央高校优秀青年教师科研创新基金（2021―2022），主持
• 中央高校基本科研业务费学科交叉创新团队（2021―2023），参与
• 国家自然科学基金青年项目（2021―2023），主持
• 甘肃省自然科学基金面上项目（2021―2022），主持
• 中央高校优秀青年教师科研创新基金（2019―2020），主持
• 姚高民生命科学基金（2018―2019），主持
• 兰州大学人才引进基金（2018―2020），主持
  

本科生课程教学

生命科学学院《生物化学》

萃英学院《合成生物学》

药学院《生物化学与分子生物学》（2019―2023）（课程负责人）

生命科学学院《生物物理学》（合讲）、《结构生物学》（合讲）

研究生课程教学

《Practical Introduction to Structural Study of Macromolecules》（课程负责人）

《结构生物学导论》（合讲）

《天然产物生物合成概论》（合讲）

Our laboratory is dedicated to studying the biosynthesis and cellular roles of tRNA modifications, with a focal point on tRNA N6-threonylcarbamoyladenosine (t6A), which is a necessary post-transcriptional modification universally found in ANN–decoding tRNAs in all the three domains of cellular life. The t6A is located 3'–adjacent to the anticodon triplet in the anticodon stem loop (ASL) of tRNAs, wherein it plays pivotal roles in preventing the U33 and A37 from unwanted Watson–Crick pairing and in constraining the structural configuration of ASL. tRNA t6A functions to enhance anticodon–codon pairing and promotes the translational fidelity. The absence tRNA t6A gravely affects cellular proteostasis and causes death of unicellular organisms, is also implicated in the growth and development of higher eukaryotes, and a set of human diseases, i.e. Galloway-Mowat Syndrome. The biosynthesis of tRNA t6A is universally accomplished by two-step consecutive reactions that are catalyzed by TsaC/Sua5 family proteins and TsaD/Kae1/Qri7 family proteins in cooperation with a varying number of regulatory proteins.

However, the molecular mechanisms and machinery workings underlying tRNA t6A biosynthesis vary substantially among different life forms and organisms. Over the past decade, we have aggregated ample knowledge and sophisticated techniques in dissecting the structure–function relationship of tRNA t6A-modifying enzymes. Though challenging, our lab is doggedly elucidating molecular mechanisms of tRNA t6A-modifying enzymes and cellular roles of tRNA t6A and a number of other hypermodified t6A derivatives (i.e. ht6A, m6t6A, ms2t6A, ct6A, ms2ct6A) in evolution and development of life, using an array of approaches and techniques in molecular biology, enzymology, structural biology, cellular biology and genetics.

Join us!

• 第八届全国大学生生命科学竞赛甘肃省一等奖、全国二等奖指导教师（2023）
  
• 兰州大学“萃英学者”特聘教授荣誉称号（2023）
• 甘肃省杰出青年基金获得者（2023）
• 第四届全国核糖核酸（RNA）青年学术会议优秀报告奖（2023）
• 兰州大学2022年本科毕业论文（设计）及临床毕业实习优秀指导教师奖（2023）
• 兰州大学生命科学学院与口腔医学院第三届青年教师联合讲课比赛三等奖（2019）

1. ❖ Fu, W., Lin, Y., Bai, M., Yao, J., Huang, C., Gao, L., Mi, N., Ma, H., Tian, L., Yue, P., Zhang, Y., Zhang, J., Ren, Y., Ding, L., Dai, L., Leung, J., Yuan, J., Zhang, W. and Meng. W. (2024) Beyond ribosomal function: RPS6 deficiency suppresses cholangiocarcinoma cell growth by disrupting alternative splicing. Acta Pharmaceutica Sinica B., 14, 3931–3948.
   
2. ❖ Zheng, X., Su, C., Duan, L., Jin, M., Sun, Y., Zhu, L. and Zhang, W. (2024) Molecular basis of A. thaliana KEOPS complex in biosynthesizing tRNA t⁶A. Nucleic Acids Res., 52, 4523–4540. ☆ In News: https://news.lzu.edu.cn/c/202403/109674.html
3. ❖ Chen, W., Jin, M. and Zhang, W. (2024) Characterization of human mitochondrial tRNA t⁶A-modifying enzyme OSGEPL1. SCIENTIA SINICA Vitae（中国科学：生命科学）, 54, 706–722.
4. ❖ Jin, M., Zhang, Z., Yu, Z., Chen, W., Wang, X., Lei, D. and Zhang, W. (2023) Structure-function analysis of an ancient TsaD–TsaC–SUA5–TcdA modular enzyme reveals a prototype of tRNA t⁶A and ct⁶A synthetases. Nucleic Acids Res., 51, 8711-8729. ☆ In News: https://news.lzu.edu.cn/c/202307/103208.htm
5. ❖ Alexander, L. T., Durairaj, J., Kryshtafovych, A., Abriata, L. A., Bayo, Y., Bhabha, G., Breyton, C., Caulton, S. G., Chen, J., Degroux, S., Degroux, S. Ekiert, D. C., Erlandsen, B. S., Freddolino, P. L., Gilzer, D., Greening, C., Grimes, J. M., Grinter, R., Gurusaran, M., Hartmann, M. D., Hitchman, C. J., Keown, J. R., Kropp, A., Kursula, P., Lovering, A. L., Lemaitre, B., Lia, A., Liu, S., Logotheti, M., Lu, S., Markusson, S., Miller, M. D., Minasov, G., Niemann, H. H., Opazo, F., Phillips, G. N., Jr., Davies, O. R., Rommelaere, S., Rosas-Lemus, M., Roversi, P., Satchell, K., Smith, N., Wilson, M. A., Wu, K. L., Xia, X., Xiao, H., Zhang, W., Zhou, Z. H., Fidelis, K., Topf, M., Moult, J. And Schwede, T. (2023) Protein target highlights in CASP15: Analysis of models by structure providers. Proteins, 91, 1571–1599.
   
6. ❖ Sartre, C., Peurois, F., Ley, M., Kryszke, M. H., Zhang, W., Courilleau, D., Fischmeister, R., Ambroise, Y., Zeghouf, M., Cianferani, S., Ferrandez, Y. and Cherfils, J. (2023) Membranes prime the RapGEF EPAC1 to transduce cAMP signaling. Nature Communications, 14(1):4157.
7. ❖ Wang, J., Gao, J., Guo, T., Huo, X., Zhang, W., Liu, J. and Wang, X. (2023) Bioinspired Total Synthesis of Complex Nucleoside Antibiotics A201A, A201D and A201E. Angew. Chem. Int. Ed. Engl., 62, e202213810.
   
8. ❖ Su, C., Jin, M. and Zhang, W. (2022) Conservation and Diversification of tRNA t⁶A-Modifying Enzymes across the Three Domains of Life. Int. J. Mol. Sci., 23, (21), 13600.
9. ❖ Guo, P., Pang, X., Wang, K., Su, P., Pan, Q., Han, G., Shen, Q., Zhao, Z., Zhang, W. and Shu, X. (2022) Nickel-Catalyzed Reductive Csp(3)-Ge Coupling of Alkyl Bromides with Chlorogermanes. Org. Lett., 24, (9), 1802-1806.
   
10. ❖ Wang, J., Zhou, J., Mao, X., Zhou, L., Chen, M., Zhang, W., Wang, E. and Zhou, X. (2022) Commonality and diversity in tRNA substrate recognition in t⁶A biogenesis by eukaryotic KEOPSs, Nucleic Acids Res., 50, 2223-2239.
11. ❖ Galicia, C., Lhospice, S., Varela, P., Trapani, S., Zhang, W., Navaza, J., Herrou, J., Mignot, T. and Cherfils, J. (2019) MglA functions as a three-state GTPase to control movement reversals of Myxococcus xanthus. Nature Communications, 10, 5300.
12. ❖ Das, S., Malaby, A., Nawrotek, A., Zhang, W., Zeghouf, M., Maslen, S., Skehel, M., Chakravarthy, S., Irving, T., Bilsel, O., Cherfils J. and Lambright, D. (2019) Structural Organization and Dynamics of Homodimeric Cytohesin Family Arf GTPase Exchange Factors in Solution and on Membranes. Structure, 27, 1782–1797.
13. ❖ Missoury, S., Plancqueel, S., Gallay, I., Zhang, W., Liger, D., Durand, D., Dammak, R., Collinet, B. and van Tilbeurgh, H. (2018) The crystal structure of the bacterial TsaB/TsaD/TsaE complex responsible for the essential t⁶A tRNA-modification. Nucleic Acids Res., 46, 5850-5860.
14. ❖ Pichard-Kostuch A., Zhang, W.,  Liger, D., Daugeron, M., Letoquart, J.,  Gallay, I.,  Forterre, P., Collinet, B.,  van Tilbeurgh, H. and Basta, T. (2018) Structure-function analysis of Sua5 protein reveals novel functional motifs required for the biosynthesis of the universal tRNA t⁶A. RNA, 24, 926-938.
15. ❖ Ferrandez, Y., Zhang, W., Peuroi, F., Akendengué, L., Blangy, A., Zeghouf, M. and Cherfils, J. (2017) Allosteric inhibition of the guanine nucleotide exchange factor DOCK5 by a small molecule. Scientific Reports, 7:14409| DOI:10.1038/s41598-017-13619-2|1-13.
16. ❖ Zhang, W., Collinet, B., Perrochia, L., Durand, D. and van Tilbeurgh, H. (2015) The ATP-mediated formation of the YgjD-YeaZ-YjeE complex is required for the biosynthesis of tRNA t⁶A in Escherichia coli. Nucleic Acids Res., 43, 1804-1817.
17. ❖ Zhang, W., Collinet, B., Graille, M., Daugeron, M.C., Lazar, N., Libri, D., Durand, D. and van Tilbeurgh, H. (2015) Crystal structures of the Gon7/Pcc1 and Bud32/Cgi121 complexes provide a model for the complete yeast KEOPS complex. Nucleic Acids Res., 43, 3358-3372.
18. ❖ Perrochia, L., Crozat, E., Hecker, A., Zhang, W., Bareille, J., Collinet, B., van Tilbeurgh, H., Forterre, P. and Basta, T. (2013) In vitro biosynthesis of a universal t⁶A tRNA modification in Archaea and Eukarya. Nucleic Acids Res., 41, 1953-1964.
19. ❖ He, J., Shi, J., Xu, X., Zhang, W., Wang, Y., Chen, X., Du, Y., Zhu, N., Zhang, J., Wang, Q. and Yang, J. (2012) STAT3 mutations correlated with hyper-IgE syndrome lead to blockage of IL-6/STAT3 signalling pathway. Journal of Biosciences, 37, 243-257.
20. ❖ Jiang, P., Xu, X., Chen, Y., Zhang, W., Serradji, N., Yang, J., Dong, C. and Wang, Q. (2010) PMS-1077, a PAF antagonist, induced differentiation of HL-60 cells with its novel activity. Cell Biology International, 34, 1227-1230.

• ❖ 第一届RNA治疗学年会⎯RNA治疗学前沿与挑战（2024.11.30―12.03，昆明）组织委员会 ☞ https://meetings.bsc.org.cn/RNAtherapeutics2024/
• ❖ 2024生物物理大会⎯生物物理前沿与人类健康（2024.07.25―07.28，兰州）组织委员会 ☞https://www.bsc.org.cn/2024/
  
• ❖ 第六届全国核糖核酸（RNA）青年学术会议（2024.06.21―06.23，长沙）组织委员会 ☞https://meeting.csbmb.org.cn/2024RNA-Youth/ (☆ In News: https://www.csbmb.org.cn/news/3985.html)
• ❖ 第十二届全国核糖核酸（RNA）学术会议（2023.12.08―12.11，上海）青年论坛召集人 ☞https://www.csbmb.org.cn/rna2023/index.html (☆ In News: https://www.csbmb.org.cn/news/3869.html)
• ❖ 参加兰州大学第二期高层次人才研修班（2023.07.24―07.28，陇南）
• ❖ 参加领航计划-青年科技领军人才国情研修班（2023.07.02―07.07，广州）
• ❖ 参加甘肃省无党派代表人士培训班（2023.05.29―06.02，北京）
  
• ❖ 举办第四届全国核糖核酸（RNA）青年学术会议（2023.04.20―04.22，兰州） ☞http://meeting.csbmb.org.cn/RNA2022
  ☆ In News: https://news.lzu.edu.cn/c/202304/99831.html
• ❖ 参加兰州大学第一期高层次人才研修班（2022.07.02―07.03，会宁）
• ❖ 参加教育部第一期高校青年教师国情教育研修班（2021.05.30―06.05，上海）