2002 - 2004 Ph.D, University of Science and Technology of China

2005 - 2006 Research Assistant, Institute of Biophysics, Chinese Academy of Sciences

2006 - 2011 Research Fellow, Research Associate, and Senior Research Scientist

Memorial Sloan-Kettering Cancer Center, New York

2011 - Principal Investigator, Institute of Biophysics, Chinese Academy of Sciences

2015 - Professor of University of Chinese Academy of Science

Wang’s Awards

2018 Beijing Science and Technology Award, second class

2018 Government special allowance

2017 Distinguished Professor of the Yangtze River Scholars Award Program

2017 HHMI international young scholar

2017 Outstanding tutor of Chinese Academy of Science

2016 The 13^thChinese young women scientist award

2016 Young and middle-aged outstanding talents, Ministry of Science and Technolog

The 9^thTanjiazhen Life Science awards(innovation)

2015 Chinese Annual Paper Awards, Cell Press

2015 Outstanding tutor of Chinese Academy of Science

Students’ Awards

2020 Cheng Zhi, Di Ao Scholarship and National master scholarship

2019 You Lilan, National master scholarship

2019 You Lilan, Special Award of Chinese Academy of Science

2018 Li Xueyan, Outstanding Award of director of Chinese Academy of Science

2017 Li Xueyan and Yin Maolu, National master scholarship

2017 Li Jiazhi, Selected to participate in the 68^thNobel Prize Winners Conference

2017 Li Jiazhi, Selected to participate in the 13^thInternational Student Forum

2016 Li Jiazhi, Outstanding Award of director of Chinese Academy of Science

2016 Li Jiazhi, National master scholarship

2016 Zhao Hongtu, Outstanding Graduates Award

2016 Chen Peng, Scholarship of University of Chinese Academy of Science

2015 Zhao Hongtu, Special Award of Chinese Academy of Science

2015 Zhao Hongtu, National master scholarship

2015 Zhao Hongtu, Director Paper Award

The main research focus of our group is to understand how small regulatory RNA or DNAmediates prokaryotic defense against invasion by foreign nucleic acids. The main focus of my work is to systematically demonstrate the mechanisms of (1) the CRISPR-Cas system and (2) Argonaut (Ago) protein-mediated RNA/DNA interference.

1. CRISPR-Cas systems

The clustered regularly interspaced short palindromic repeats (CRISPR), together with CRISPR-associated (Cas) proteins form the microbial adaptive immune system that protects against invading phages and plasmids. The CRISPR-Cas system is a RNA-guided immune system found in nearly half of all bacteria studied, as well as in the majority of archaea. Our research in this area includes the molecular mechanism of spacer acquisition, pre-crRNA processing and RNA-guided DNA/RNA cleavage.The overall goal of our studies of the CRISPR-Cas system is to gain important insights into the structural-functional relationship of the processes prokaryotes use to fight invading nucleic acids.

2. Ago protein-mediated DNA interference

RNA interference is a conserved biological response to double-stranded RNA that regulates gene expression. The response is mediated by small interfering RNAs (siRNAs), which guide the sequence-specific degradation of cognate messenger RNAs (mRNAs).Ago protein is a key component in the RNA interference pathway. Recent bioinformatics analyses suggest that prokaryotic Ago plays a number of critical roles in the anti-viral defense system of bacteria. Unlike its eukaryotic counterpart where mRNA interference is mediated by siRNA, several pAgo proteins have been shown to perform either RNA-guided or DNA-guided interference of DNA.Our long-term goals are to structurally characterize and mechanistically define events associated with RNA or DNA interference.

1. Huang X, Sun W, Cheng Z, Chen M, Li X, Wang J, Sheng G*, Gong W* andWang Y*. Structural basis for two metal-ion catalysis of DNA cleavage by Cas12i2.Nature Communications, 2020.10, online.

2. Sun W^#, Yang J^#, Cheng Z^#, Amrani N, Liu C, Wang K, Ibraheim R, Edraki A, Huang X, Wang M, Wang J, Liu L, Sheng G, Yang Y, Lou J, Sontheimer E*, andWang Y*. Structures of Neisseria meningitidis Cas9 Complexes in Catalytically Poised and Anti-CRISPR-Inhibited States.Molecular Cell, 2019, 76(6): 938-952.

3. You L, Ma J, Wang J, Artamonova D, Wang M, Liu L, Xiang H, Severinov K, Zhang X*,Wang Y*. Structure Studies of the CRISPR-Csm Complex Reveal Mechanism of Co-transcriptional Interference.Cell, 2019, 176, 239–253.

4. Liu L, Yin M, Wang M,Wang Y*. Phage AcrIIA2 DNA Mimicry: Structural Basis of the CRISPR and Anti-CRISPR Arms Race.Molecular Cell, 2019, 73, 611–620.

5. Lei J, Sheng G, Peter Pak-Hang Cheung, Wang S, Li Y, Gao X, Zhang Y*,Wang Y*, Huang X*. Two symmetric arginine residues play distinct roles in Thermus thermophilus Argonaute DNA guide strand-mediated DNA target cleavage,PNAS, 2019，116: 845–853.

6. Chang L^#, Sheng G^#, Zhang Y^#, Shao S,Wang Y*and Sun Y*. AgoFISH: cost-effective in situ labelling of genomic loci based on DNA-guided dTtAgo protein.Nanoscale Horizons, 2019, 4:918-923.

7. Thavalingam A, Cheng Z, Garcia B, Huang X, Shah M, Sun W, Wang M, Harrington L, Hwang Sungwon Y, Reyes H, Sontheimer E, Doudna J, Davidson A, Moraes T*,Wang Y*, Maxwell K*. Inhibition of CRISPR-Cas9 ribonucleoprotein complex assembly by anti-CRISPR AcrIIC2.Nature Commun., 2019, 26;10(1):2806.

8. Yin M, Wang J, Wang M, Li X, Zhang M, Wu Q,Wang, Y.Molecular mechanism of directional CTCF recognition of a diverse range of genomic sites.Cell Research, 2017, 27(11):1365-1377.

9. Liu L, Li X, Ma J, Li Z, You L, Wang J, Wang M, Zhang X,Wang, Y.The Molecular Architecture for RNA-Guided RNA Cleavage by Cas13a.Cell, 2017. 170(4):714-726.

10. Sheng G, Gogakos T, Wang J, Zhao, H, Serganov A, Juranek S, Tuschl T, Patel D,Wang, Y.Structure/cleavage-based insights into helical perturbations at bulge sites within T. thermophilus Argonaute silencing complexes.Nucleic Acids Res.2017, 45(15):9149-9163.

11. Liu L, Li X, Wang J, Yin M, Chen P, Wang M, Li J, Sheng G,Wang Y.Two Distant Catalytic Sites Are Responsible for C2c2 RNase Activities.Cell.2017,168:121-134.

12. Liu L, Chen P, Wang M, Li X, Wang J, Yin M,Wang Y.C2c1-sgRNA Complex Structure Reveals RNA-guided DNA Cleavage Mechanism.Molecular Cell.2017, 65.

13. Swarts D, Szczepaniak M, Sheng G, Chandradoss S, Zhu Y, Timmers E, Zhang Y, ZhaoH, Lou J,Wang Y,Joo C and Oost J. Autonomous Generation and Loading of DNA Guides by Bacterial Argonaute，Molecular Cell,2017, 65(6):985-998.

14. Wang J, Ma J, Cheng Z, Meng X, You L, Wang M, Zhang X,Wang, Y.A CRISPR evolutionary arms race: structural insights into viral anti-CRISPR/Cas responses.Cell Research.2016, 26:1165–1168.

15. Wang, J., Li, J., Zhao, H., Sheng, G., Wang, M., Yin, M. &Wang, Y., Structural and Mechanistic Basis of PAM-Dependent Spacer Acquisition in CRISPR-Cas System.Cell.2015, 163: 840-853.

16. Zhao, H., Sheng, G., Wang, J., Wang, M., Bunkoczi, G., Gong, W., Wei, Z. &Wang, Y.“Crystal structure of the RNA-guided immune surveillance Cascade complex in Escherichia coli”,Nature.2014, 151: 147-150.

17. Swarts, D. C., Makarova, K.,Wang, Y.,Nakanishi, K., Ketting, R., Koonin, E., Patel, D. J. & Oost, van der, J., “The evolutionary journey of Argonaute proteins”,Nature structural & molecular biology, 2014, 21: 743-753.

18. Swarts, D. C., Jore, M. M., Westra, E. R., Zhu, Y., Janssen, J. H., Snijders, A. P.,Wang, Y.,Patel, D. J., Berenguer, J., Brouns, S. J.J. & Oost, van der, J. "DNA-guided DNA interference by a prokaryotic Argonaute",Nature, 2014, 507: 258-261.

19. Sheng, G., Zhao, H., Wang, J., Rao, Y., Tian, W., Swarts, D. C., van der Oost, J., Patel, D. J. andWang, Y. "Structure-based cleavage mechanism of Thermus thermophilus Argonaute DNA guide strand-mediated DNA target cleavage."Proc Natl Acad Sci U S A.2014, 111(2): 652-657.

20. Rüdel S,Wang, Y, Lenobel R, K?rner R, Hsiao HH, Urlaub H, Patel D, Meister G. Phosphorylation of human Argonaute proteins affects small RNA binding.Nucleic Acids Res.2011,39:2330-43.

21.Wang, Y., Ludwig J., Schuberth C., Goldeck M., Schlee M., Li H., Juranek S., Sheng G., Micura R., Tuschl T., Hartmann G., Patel D., Structural and functional insights into 5'-ppp RNA pattern recognition by the innate immune receptor RIG-I.Nat Struct Mol Biol.2010, 17:781-7.. 2010, 17:781-7.

22.Wang, Y, Juranek S, Li H, Sheng G, Tuschl T, Patel DJ. Nucleation, propagation and cleavage of target RNAs in Ago silencing complexes.Nature.2009, 461:754-761.

23.Wang, Y, Juranek S, Li H, Sheng G, Tuschl T, Patel DJ. Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex.Nature.2008, 56:921-926.

24.Wang, Y, Sheng G, Juranek S, Tuschl T, Patel DJ., Structure of the guide-strand-containing argonaute silencing complex.Nature. 2008, 456:209-213.

25.Wang, Y, Liu L, Wei Z, Cheng Z, Lin Y, Gong W. Seeing the process of histidine phosphorylation in human bisphosphoglycerate mutase.J Biol Chem.2006, 281:39642-8.

26.Wang, Y, Wei Z, Liu L, Cheng Z, Lin Y, Ji F, Gong W. Crystal structure of human B type phosphoglycerate mutase bound with citrate.Biochem. Biophys. Res. Commun. 2005, 331:1207-15.

27.Wang, Y, Wei Z, Bian Q, Cheng Z, Wan M, Liu L, Gong W，Crystal structure of human bisphosphoglycerate mutase,J. Biol. Chem.2004, 279: 39132-8.

(From Yanli Wang, November 16, 2020)