张跃林博士 - 科学研究 - 北京生命科学研究所

张跃林博士

北京生命科学研究所高级研究员

Yuelin Zhang, Ph.D.

Associate Investigator, NIBS, Beijing, China

教育经历

Education

1989	复旦大学遗传学及遗传工程专业学士
	B.S., Genetics and Genetic Engineering, Fudan University, China
1995	美国俄克拉荷马州立大学生物化学及分子生物学专业理学博士
	Ph.D., Biochemistry and Molecular Biology, Oklahoma State University

工作经历

Professional Experience

2011-2012

北京生命科学研究所高级研究员

Associate Investigator, National Institute of Biological Sciences, Beijing, China

2005-2011	北京生命科学研究所研究员 Assistant Investigator, National Institute of Biological Sciences, Beijing, China
2001-2005	英属哥伦比亚大学，Michael Smith 实验室荣誉助教授
	Assistant Professor (honorary appointment), Michael Smith Laboratories, University of British Columbia
2000-2001	Maxygen公司农业基因项目主管
	Group Leader of Agricultural Genomics, Maxygen, Inc.
1998-2000	Tellus Genetics公司实验室主任
	Co-founder and Research Director, Tellus Genetics, Inc.
1998-1999	杜克大学生物学系发育、细胞及分子生物学部博士后研究助理
	Postdoctoral Research Associate, Developmental, Cell and Molecular Biology Group, Department of Biology, Duke University
1995-1998	北卡罗莱纳大学化学系博士后研究助理
	Postdoctoral Research Associate, Department of Chemistry, University of North Carolina, Chapel Hill

研究概述：

识别和抵抗微生物的侵染对于多细胞生物的存活是至关重要的。在此过程中，先天性免疫起着关键性作用。动物中的受体（如Toll样受体、Nod蛋白）对病原配体的识别诱导了先天性免疫反应；在植物中，抗病基因产物对病原无毒信号的识别启动了下游的信号级联反应，从而限制了病原的增殖和扩散。植物的大多数抗病蛋白与动物的 Nod蛋白具有结构上的同源性。越来越多的研究表明，二者下游的信号通路也非常相似。我们的研究主要分为两个方面：

1. 抗病蛋白介导的免疫反应: R蛋白根据结构差异可以分为NBS-LRR(包括CC-NBS-LRR和TIR-NBS-LRR)、LRR-RLK和LRR-RLP。我们在组成型抗病的突变体bir1-1，snc2-1D，snc4-1D，snc6-1D， mkk1 mkk2背景下进行抑制子筛选，从而找到R基因介导的免疫反应的突变体。通过图位克隆和全基因组测序的方法鉴定到R蛋白介导的免疫反应的重要元件。利用遗传学、生物化学、细胞生物学等方法阐释这些重要元件在分子水平以及个体水平的功能，最终希望通过生物信息学和系统生物学分析构建抗病蛋白介导的免疫反应信号传导网络。

2. 系统获得性抗性: 抗病蛋白介导的抗病反应通常导致局部性细胞凋亡，在植物学上称为过敏反应。系统获得性抗性是过敏反应之后的次级反应，它赋予植物对广谱病原体的非特异性的系统抗性 (SAR)。由于缺少一个快速高通量检测SAR的方法，SAR这条信号通路的研究受到很大限制。我们已经建立了一套快速灵敏并且高通量检测SAR的系统。通过正向遗传学和反向遗传学筛选我们希望获得SAR过程中包括局部信号产生、信号由局部到其他部位传递及信号被接收和传导相关的突变体。通过图位克隆和全基因组测序鉴定到突变位点，再结合表型分析、生物化学、细胞生物学功能分析这些新基因的功能，从而全面了解SAR信号通路的各个层面。

Research Description

Sensing and defending against microbial infections is essential to the survival of all multicellular organisms. Innate immunity plays a key role in this process. Across the animal kingdom, innate immunity relies on the recognition of microbial ligands by “pattern recognition receptors” such as Toll-like receptors and nucleotide-binding oligomerization domain (Nod) proteins. In plants, recognition of an avirulence signal from the pathogen by a cognate host resistance (R) gene product leads to activation of downstream signal transduction cascades and restriction of pathogen colonization. My research is focused mainly on the following two areas.

1. Immunity mediated by plant Resistance (R) proteins

There are three major classes of R genes in plants. The largest class encodes intracellular NB-LRR type R proteins with structural similarity to Nod proteins. The other two classes of R genes encode transmembrane receptor-like kinases (RLKs) and receptor-like proteins (RLPs). We first obtained a series of mutants such as bir1-1, snc2-1D, snc4-1D, snc6-1D and mkk1 mkk2 that constitutively activate immunity mediated by these three classes of R proteins. Subsequently we carried out suppressor screens of these mutants to look for components downstream of the R proteins. Cloning the suppressor genes and analyzing biochemical functions of proteins encoded by them will help us build the signal transduction network of plant immunity.

2. Systemic Acquired Resistance (SAR)

Localized programmed cell death, termed the hypersensitive response (HR), is often associated with R-gene-mediated resistance. Systemic acquired resistance (SAR) is a secondary resistance response that follows the R gene-mediated HR and provides general systemic resistance against a broad-spectrum of pathogens. We have successfully developed a high-throughput assay for SAR. The new assay is very sensitive and reproducible. Using this assay, we have carried out both forward and reverse genetic screens to look for mutants with defects in SAR. Identification and characterization of genes required for SAR will help us understand the underlining mechanisms of SAR.

Publications (*corresponding author)

1. Zhang, Y., Xu, S., Ding, P., Wang, D., Cheng, Y., He, J., Gao, M., Xu, F., Li, Y., Zhu, Z., Li, X., and Zhang, Y.* 2010. Control of salicylic acid synthesis and systemic acquired resistance by two members of a plant-specific family of transcription factors. Proceedings of the National Academy of Sciences (track II). 107(42):18220-18225.

2. Li, Y., Li, S., Bi, D., Cheng, Y., Li, X. and Zhang, Y.* 2010. SRFR1 negatively regulates plant NB-LRR Resistance protein accumulation to prevent autoimmunity. PLoS PLoS Pathogens, 6 (9), e1001111.

3. Zhang, Y., Yang, Y., Fang, B., Gannon, P., Ding, P., Li, X., and Zhang, Y.*2010.

snc2-1D activates receptor like protein-mediated immunity transduced through WRKY70. Plant Cell, 2010 Sep 14. (Epub ahead of print).

4. Zhu, Z., Xu, F., Zhang, Y., Cheng, Y., Wiermer, M., Li, X., and Zhang, Y.*2010. Arabidopsis Resistance protein SNC1 activates immune responses through association with a transcriptional co-repressor. Proceedings of the National Academy of Sciences (track II). 107(31):13960-13965.

5. Bi, D., Cheng, Y., Li, X., and Zhang, Y.* 2010. Activation of plant immune responses by a gain-of-function mutation in an atypical receptor-like kinase. Plant Physiology, 153(4):1771-1779.

6. Li, Y., Tessaro, M., Li, X., and Zhang, Y.* 2010. Regulation of the expression of plant Resistance gene SNC1 by a Protein with a Conserved BAT2 Domain. Plant Physiology, 153(3):1425-1434.

7. Zhang, J., Li, W., Xiang, T., Liu, Z., Laluk, K., Ding, X., Zou, Y., Gao, M., Zhang, X., Chen, S., Mengiste, T., Zhang, Y., and Zhou, J.M. 2010. Receptor-like cytoplasmic kinases integrate signaling from multiple plant immune receptors and are targeted by a Pseudomonas syringae effector.Cell Host & Microbe 7:290-301.

8. Gao, M., Wang, X., Wang, D., Xu, F., Ding, X., Zhang, Z., Bi, D., Cheng, Y.T., Chen, S., Li, X., and Zhang, Y*. 2009. Regulation of cell death and innate immunity by two receptor-like kinases in Arabidopsis. Cell Host & Microbe6:34-44.

9. Cheng, Y.T., Germain, H., Wiermer, M., Bi, D., Garcia, A.V., Wirthmueller, L., Despres, C., Parker, J.E., Zhang, Y., and Li, X. 2009. MOS7 is required for plant innate immunity and nuclear accumulation of defense regulators.Plant Cell 21:2503-2516.

10. Monaghan, J., Xu, F., Gao, M., Zhao, Q., Palma, K., Long, C., Chen, S.,Zhang, Y., and Li, X. 2009. Two Prp19-like U-box proteins in the MOS4-associated complex play redundant roles in plant innate immunity. PLoS Pathogens 5, e1000526.

11. Xia, X., Zhu, Z., Hao, L., Chen, J.G., Xiao, L., Zhang, Y., and Li, X. 2009. Negative Regulation of Systemic Acquired Resistance by Replication Factor C Subunit 3 in Arabidopsis. Plant Physiology 150:2009-2017.

12. Gao, M., Liu, J., Bi, D., Zhang, Z., Cheng, F., Chen, S., and Zhang, Y*. 2008. MEKK1, MKK1/MKK2 and MPK4 function together in a mitogen-activated protein kinase cascade to regulate innate immunity in plants.Cell Research 18:1190-1198. (Cover story)

13. Goritschnig, S., Weihmann, T., Zhang, Y., Fobert, P., McCourt, P., Gruissem, W., and Li, X. 2008. A novel role for protein farnesylation in plant innate immunity. Plant Physiology 148:348-357.

14. Palma, K., Zhao, Q., Cheng, Y.T., Bi, D., Monaghan, J., Cheng, W., Zhang, Y., and Xin Li. 2007. Regulation of plant innate immunity by three proteins in a complex conserved across the plant and animal Kingdoms.Genes & Development 21:1484-1493.

15. Wiermer, M., Palma, K., Zhang, Y., and Li, X. 2007. Should I stay or should I go? Nucleocytoplasmic trafficking in plant innate immunity.Cellular Microbiology 9:1880-1890.

16. Goritschnig, S., Zhang, Y., and Li, X. 2007. The ubiquitin pathway is required for innate immunity in Arabidopsis. Plant Journal 49: 540-551.

17. Zhang, Y.*, Cheng, Y.T., Qu, N., Zhao, Q., Bi, D., and Li, X. 2006. Negative regulation of defense responses in Arabidopsis by two NPR1 paralogs.Plant Journal 48: 647-656.

18. Zhang, Y., Cheng, Y., Bi, D., Palma, K., and Li, X. 2005. MOS2, a protein containing G-patch and KOW motifs, is essential for innate immunity in Arabidopsis thaliana. Current Biology 15:1936-1942.

19. Zhang, Y. and Li, X. 2005. A Putative Nucleoporin 96 is required for both basal defense and constitutive resistance responses mediated by snc1.Plant Cell 17: 1306-1316.

20. Hepworth, S.?, Zhang, Y. ? (co-first author), McKim, S., Li, X., and Haughn, G.W. 2005. BLADE-ON-PETIOLE-Dependent Signaling Controls Leaf and Floral Patterning in Arabidopsis. Plant Cell 17:1434-1448.

21. Palma, K., Zhang, Y., and Li, X. 2005. An Importin alpha Homolog, MOS6, Plays an Important Role in Plant Innate Immunity. Current Biology 15: 1129-1135.

22. Li, X. and Zhang, Y. 2005. Novel reverse genetics tools in plant functional genomics. Book chapter for Plant Functional Genomics, edited by Dario Leister, the Haworth Press, Inc.

23. Miles, G.P., Samuel, M.A., Zhang, Y., and Ellis, B.E. 2005. RNA interference-based (RNAi) suppression of AtMPK6, an Arabidopsis mitogen-activated protein kinase, results in hypersensitivity to ozone and misregulation of AtMPK3. Environmental Pollution 138:230-237.

24. Monte, E., Tepperman, J.M., Al-Sady, B., Kaczorowski, K.A., Alonso, J.M., Ecker, J.R., Li, X., Zhang, Y. and Quail PH. 2004. The phytochrome-interacting transcription factor, PIF3, acts early, selectively, and positively in light-induced chloroplast development. Proceedings of the National Academy of Sciences 101: 16091-16098.

25. Zhang, Y., Goritschnig, S., Dong, X., and Li, X. 2003. A gain-of-function mutation in a plant disease resistance gene leads to constitutive activation of downstream signal transduction pathways in the snc1 mutant. Plant Cell 15: 2636-2646.

26. Zhang, Y.*, Tessaro, M., Lassner M., and Li, X. 2003. Knockout Analysis of Arabidopsis TGA2, TGA5 and TGA6 revealed their redundant and essential roles in systemic acquired resistance. Plant Cell 15: 2647-2653.

27. Monte E., Alonso, J.M., Ecker, J.R., Zhang, Y., Li, X., Young, J., Austin-Phillips, S., and Quail P.H. 2003. Isolation and Characterization of phyC Mutants in Arabidopsis Reveals Complex Crosstalk between Phytochrome Signaling Pathways. Plant Cell 15: 1962-1980.

28. Li, X. and Zhang, Y.* 2002. Reverse genetics by fast neutron mutagenesis in higher plants. Functional & Integrative Genomics 2: 254-258.

29. Li, X., Song, Y., Century, K., Straight, S., Ronald, P., Dong, X., Lassner, M., and Zhang, Y.* 2001. A fast neutron deletion mutagenesis-based reverse genetics system for plants. Plant Journal 27: 235-242.

30. Li, X., Clarke, J.D., Zhang, Y., and Xinnian Dong. 2001. Activation of an EDS1-Mediated R-Gene Pathway in the snc1 Mutant Leads to Constitutive, NPR1-Independent Pathogen Resistance. Molecular Plant-Microbe Interactions 14: 1131-1139.

31. Dong, X., Li, X., Zhang, Y., Fan, W., Kinkema, M., and Clarke, J. 2001. Regulation of systemic acquired resistance by NPR1 and its partners.Novartis Found Symp 236: 165-73.

32. Zhang, Y., Fan, W.H., Kinkema, M., Li., X., and Dong, X. 1999. Interactions of NPR1 with basic leucine zipper protein transcription facters that bind sequences required for salicylic acid induction of the PR-1 gene.Proceedings of the National Academy of Sciences 96: 6523-6528.

33. Li, X., Zhang, Y., Clarke, J.D., Li, Y., and Dong, X. 1999. Identification and cloning of a negative regulator of systemic acquired resistance, SNI1, through a screen for suppressors of npr1-1. Cell 98: 329-339.

34. Zhang, Y., Lartey, R.T., Voss, T.C., and Melcher, U. 1999. Limitation to tobacco mosaic virus infection of turnip. Archives of Virology 144(5): 957-971.

35. Bullard, J.M., Cai, Y.C., Zhang, Y., and Spremulli, L.L. 1999. Effects of domain exchange between E. coli and mammalian mitochondrial EF-Tu on interactions with guanine nucleotides, aminoacyl-tRNA and Ribosomes. B.B.A. 1446:102-114.

36. Zhang, Y. and Spremulli, L.L. 1998. Roles of residues in mammalian mitochondrial elongation factor Ts in the interaction with mitochondrial and bacterial elongation factor Tu. Journal of Biological Chemistry 273 (43): 28142-28148.

37. Zhang, Y., Yu, N.J., and Spremulli, L.L. 1998. Mutational analysis of the roles of residues in E. coli elongation factor Ts in the interaction with elongation factor Tu. Journal of Biological Chemistry 273(8): 4556-4562.

38. Zhang, Y. and Spemulli, L.L. 1998. Identification and cloning of human mitochondrial translational release factor1 and ribosome recycling factor. B.B.A. 1443: 245-250.

39. Zhang, Y., Sun, V., and Spremulli, L.L. 1997. Role of domains of E. coli and mitochondrial elongation factor Ts in the interactions with bacterial and mitochondrial elongation factor Tu. Journal of Biological Chemistry 272(35): 21956-21963.

40. Zhang, Y., Li, X., and Spremulli, L.L. 1996. Roles of the conserved aspartate and phenylalanine residues in prokaryotic and mitochondrial elongation factor Ts in guanine nucleotide exchange. FEBS Letters 391: 330-332.