袁于人

    

袁于人  高级研究员

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研究工作经历

2011/03至今: 苏州工业园区新国大研究院,高级研究员,实验室主任。

2012/01至今:新加坡国立大学生物系副教授(终身)

2006/07-2011/12:新加坡国立大学生物系助理教授

2006/07-2012/06:新加坡淡马锡生命科学院首席研究员

2001/05-2006/06:美国纽约斯隆-凯瑟琳癌症研究心,副研究员/高级研究员

1998/08-2001/04:哥伦比亚大学博士后研究员


受教育经历

1995/09-1998/07:中国科学院上海细胞生物学研究所 获博士学位

1992/09-1995/07:中国科学院上海有机化学研究所 获硕士学位

1988/09-1992/07:苏州大学化学系 获学士学位 


电邮dbsyya@nusri.cn; dbsyya@nus.edu.sg


研究领域

我们团队的研究工作主要集中在两个方面:

1. 小RNA作用机制

无论在原核还是真核细胞中,小RNA在基因调控中都起了很重要的作用。在这些信息调控通路中,我们的研究工作主要集中在和小RNA相互作用的一些蛋白以及与之形成复合物的分子结构方面的研究。结合蛋白质组学、生物物理学和基因组学方面的手段,我们正在研究拟南芥和人类的“小RNA诱导的基因沉默复合物前体”的结构特征和细菌中CRISPR的作用机制,这些研究将从新的视角理解小RNA在体内外的作用机制。

2. 利用X-射线、核磁共振和冷冻电镜三维结构重建等手段研究宿主和病原体之间的相互作用

除了原核生物和真核生物以外,病毒是生命的另外一种存在形式。研究表明,很多病毒危及到人类和动植物的生存。结合结构生物学和蛋白质工程学等方面的研究手段,我们主要研究病毒结构、病毒抗原中和表位的表征和基于病毒的疫苗研发等。通过对全病毒高分辨率结构的解析,结合高分辨率的分子影像技术直接进行单分子水平上的病毒侵染过程的可视化研究。我们的研究,对于理解病毒的侵染途径和预防病毒感染提供了新的思路。我们已在一些重要的兽用和人用疫苗的开发方面取得了重大进展。


代表性论文

1. Guo W, Liew J, Yuan YA. (2013) Structural insights into arms race between host and virus along RNA silencing pathways in Arabidopsis thaliana. Biological Review. (accepted)

2. Gu Y, Cao F, Wang L, Hou W, Zhang J, Hew CL, Li S, Yuan YA, Xia N. (2013) Structure of a Novel Shoulder-to-Shoulder p24 Dimer in Complex with the Broad-Spectrum Antibody A10F9 and Its Implication in Capsid Assembly. PLoS One. 8(4):e61314.

3. Yuan Z, Yin B, Wei D, Yuan YA. (2013) Structural basis for cofactor and substrate selection by cyanobacterium succinic semialdehyde dehydrogenase. J Struct Biol. 182(2):125-35.

4. Fu Q, Yuan YA. (2013) Structural insights into RISC assembly facilitated by dsRNA-binding domains of human RNA helicase A (DHX9). Nucleic Acids Res. 41(5):3457-70.

5. Machida S, Yuan YA. (2013) Crystal Structure of Arabidopsis thaliana Dawdle Forkhead-Associated Domain reveals a conserved phospho-threonine recognition cleft for Dicer-like1 binding. Mol Plant. 2013 Jan 11. [Epub ahead of print]

6. Sun Y, Wang C, Yuan YA, He CY. (2012) An intra-cellular membrane junction mediated by flagellum adhesion glycoproteins links flagellum biogenesis to cell morphogenesis in Trypanosoma brucei. J Cell Sci. 2012 Nov 23.

7. Zha X, Xia Q, Yuan YA. (2012) Structural insights into small RNA sorting and mRNA target binding by Arabidopsis Argonaute Mid domains. FEBS Lett. 586(19):3200-7.

8. Hou Y, Xia Q, Yuan YA. (2012) Crystal structure of BmNPV ORF75 reveals a pseudo-dimer of sulfhydryl oxidase domains with a putative substrate binding pocket. J Gen Virol. 93(10):2142-51.

9. Zhang T, Cheng T, Wei L, Cai Y, Yeo AE, Han J, Yuan YA, Zhang J, Xia N. (2012) Efficient inhibition of HIV-1 replication by an artificial polycistronic miRNA construct. Virol J. 9:118.

10. Li FJ, Shen Q, Wang C, Sun Y, Yuan YA, He CY. (2012) A role of autophagy in Trypanosoma brucei cell death. Cell Microbiol. 14(8):1242-56.

11. Chatterjee K, Blaby IK, Thiaville PC, Majumder M, Grosjean H, Yuan YA, Gupta R, de Crécy-Lagard V. (2012) The archaeal COG1901/DUF358 SPOUT-methyltransferase members, together with pseudouridine synthase Pus10, catalyze the formation of 1-methylpseudouridine at position 54 of tRNA. RNA. 18(3):421-33.

12. Liu X, Yuan Z, Yuan YA, Lin J, Wei D. (2011) Biochemical and structural analysis of Gox2181, a new member of the SDR superfamily from Gluconobacter oxydans. Biochem Biophys Res Commun. 415(2):410-5.

13. Machida S, Chen HY, Yua n YA. (2011) Molecular insights into miRNA processing by Arabidopsis thaliana SERRATE.Nucleic Acids Research 39(17):7828-36.

14. Yang X, Tan SH, Teh YJ, Yuan YA. (2011) Structural implications into dsRNA binding and RNAi suppression by Rice Hoja Blanca Tenuivirus NS3. RNA. 17(5):903-11.

15. Wang M, Soyano T, Machida S, Yang JY, Jung C, Chua NH, Yuan YA. (2011) Molecular insights into plant cell proliferation disturbance by Agrobacterium protein 6b. Genes Dev. 25(1):64-76.

16. Chen HY, Yuan YA. (2010) Crystal structure of Mj1640/DUF358 protein reveals a putative SPOUT-class RNA methyltransferase. J Mol Cell Biol. 2(6):366-74.

17. Qin H, Chen F, Huan X, Machida S, Song J, Yuan YA. (2010) Structure of Arabidopsis thaliana DCL4 DUF283 domain reveals a non-canonical double-stranded RNA-binding fold for protein-protein interaction. RNA 16, 474-481.

18. Yang SW, Chen HY, Yang J, Machida S, Chua NH, Yuan YA. (2010) Structure of Arabidopsis HYPONASTIC LEAVES1 and its molecular implications for miRNA processing. Structure 18, 594-605.

19. Yang J, Yuan YA. (2009) A structural perspective of the protein-RNA interactions involved in virus-induced RNA silencing and its suppression. Biochim. Biophys. Acta. 1789, 642-652.

20. Cheng A, Speir JA, Yuan YA, Johnson JE, Wong SM. (2009) Preliminary X-ray data analysis of crystalline hibiscus chlorotic ringspot virus. Acta Crystallogr Sect F Struct Biol Cryst Commun 65(Pt 6):589-93.

21. Cheng A. Wong SM, Yuan YA. (2009) Structural Basis for dsRNA Recognition by NS1 protein of Influenza Virus A. Cell Research 19, 187-195. (Cover feature)

22. Lin C, Yuan YA. (2008) Structural insights into histone H3 lysine 56 acetylation by Rtt109. Structure 16(10):1503-10.

23. Chen HY, Yang J, Lin C, Yuan YA. (2008) Structural basis for RNA-silencing suppression by Tomato aspermy virusprotein 2b. EMBO reports 9, 754-760. (Cover feature, selected and reviewed by Faculty 1000 Biology)

24. Zhang, X, Yuan, Y.R. (Adam), Pei, Y. et al. and Chua, N.H. (2006) Cucumber mosaic virus-encoded 2b suppressor inhibits Arabidopsis Argonaute1 cleavage activity to counter plant defense. Genes & Dev. 20, 3255-3268.

25. Yuan, Y.R. (Adam), Pei, Y., Chen, H.Y., et al. and Patel, D.J. (2006) A potential protein-RNA recognition event along the RISC-loading pathway from the structure of A. aeolicus Argonaute with externally-bound siRNA. Structure 14, 1557-1565.

26. Yuan, Y.R. (Adam), Pei, Y., Ma, J.B., et al. and Patel, D.J. (2005) Crystal structure of A. aeolicus Argonaute, a site-specific DNA-guided endoribonuclease, provides insights into RISC-mediated mRNA cleavage. Molecular Cell 19, 405-419. (Feature article)

27. Ma, J.B., Yuan, Y.R. (Adam), Meister, G., et al. and Patel, D.J. (2005) Structural basis for 5'-end-specific recognition of guide RNA by the A. fulgidus Piwi protein. Nature, 434, 666-670.


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