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王忆平

邮  箱: wangyp@pku.edu.cn

职  称:教授

办公室地址:北京市海淀区颐和园路5号,北京大学,生物技术楼,100871

实验室地址:北京市海淀区颐和园路5号,北京大学,生物技术楼,100871

  • 个人简介
  • 科研领域
  • 代表性论文

教育经历:

1992,博士学位,微生物学系,爱尔兰国立大学科克学院;
1984,学士学位,分子生物学专业,中国科学技术大学生物系;

荣誉奖励:

1999年国家杰出青年基金获得者

工作经历:

1999.7-至今,教授,北京大学新葡亰8814网站是多少
1994.8-1999.6,副教授,北京大学新葡亰8814网站是多少
1993,博士后,法国巴斯德研究所分子生物学部
1991-1992,Research Scientist,爱尔兰Bio-Research Ireland Food Biotechnology Center
1986,访问学者,德国比勒费尔德大学遗传学系
1984-1985,实习研究员,中科院植物研究所固氮研究室

社会服务工作:

1999年国家杰出青年基金获得者

杂志任职:

2021-2014, Editorial Board Member with Current Opinion in Microbiology 2015-now, Editorial Board Member with Research in Microbiology
      本实验室主要兴趣在于:    
  多年来,本实验室的工作得到国际同行的认可。主要得到国家自然科学基金、国家科技部“863”、“973”项目基金、国家教育部基金资助、中法先进合作项目、Human Frontier Science Program等项目资助。主要工作包括:大肠杆菌及相关细菌中的基因调控网络,尤其是碳代谢和氮代谢的调控偶联;大肠杆菌及相关细菌中的基因调控机理;植物与微生物相互作用的分子生物学及功能基因组学研究;生物修复领域的研究(功能基因的分离);合成生物学及生物固氮;大肠杆菌定量生物学研究等。取得的主要成就有,发现原核基因表达调控中碳代谢及氮代谢之间的新的偶联作用及其分子机理;发现DNA物理特性参与基因表达调控(该成果被国际知名学术网站Faculty of 1000 推荐);提出了激活蛋白-启动子DNA-σ54-RNA聚合酶所形成的激活复合体的“三明治”结构模型(该成果被国际知名学术网站Faculty of 1000 推荐;使用合成生物学方法,我们使用T7 RNA聚合酶表达系统替代原有的σ54 RNA聚合酶对固氮基因簇的转录调控,绕开了原有固氮基因簇对转录调控系统中14种调控蛋白的依赖,为最终实现固氮基因向真核系统的转移打下坚实的基础;以肺炎克氏杆菌钼铁固氮基因簇为底盘,成功的在大肠杆菌中构建了杂合的铁铁固氮酶体系,从而在不损失酶活的前提下,成功构建了杂合的只含有10个结构基因的最小铁铁固氮酶体系(Yang et al. 2014,PNAS);证明来源于植物叶绿体和根部白体的电子传递链模块能够功能替代钼铁及铁铁固氮酶系统中负责电子传递的原始模块,提供底物还原所需的还原力的工作(Yang and Xie et al. 2017, PNAS。该论文被PNAS期刊推荐为“From the cover”封面文章);以及将极其复杂的需要十几个甚至几十个基因协同表达的钼铁固氮酶系统简化为五个编码Polyprotein的巨型基因,并证明其高活性可支持大肠杆菌以氮气作为唯一氮源生长的工作(Yang and Xie et al. 2018, PNAS。该论文被PNAS期刊推荐为“From the cover”封面文章),以上研究具有里程碑式的意义,为最终实现固氮基因向真核系统的转移打下坚实的基础。
1. Bueno Batista, M. *, Brett, P., Appia-Ayme, C., Wang, Y.P. *, and Dixon, R. * (2021) Disrupting hierarchical control of nitrogen fixation enables carbon-dependent regulation of ammonia excretion in soil diazotrophs. PLoS Genet. 17(6):e1009617. doi: 10.1371/journal.pgen.1009617. Epub ahead of print. PMID: 34111137.
2.Xiang, N., Guo, C., Liu, J., Xu, H., Dixon, R.,* Yang, J.,* and Wang, Y.P.* (2020) Using synthetic biology to overcome barriers to stable expression of nitrogenase in eukaryotic organelles. Proc Natl Acad Sci USA. 117 (28): 16537-16545. doi:10.1073/pnas.2002307117
3.Jiang, F., Li, N., Wang, X., Cheng, J., Huang, Y., Yang, Y., Yang, J., Cai, B., Wang, Y.P., Jin, Q., and Gao, N. (2019) Cryo-EM structure and assembly of an extracellular contractile injection system. Cell 177, 1–14. doi: 10.1016/j.cell.2019.02.020.
4. Yang, J., Xie, X., Xiang, N., Dixon, R.,* and Wang, Y.P.* (2018) A polyprotein strategy for stoichiometric assembly of nitrogen fixation components for synthetic biology. Proc Natl Acad Sci U S A. 201804992; DOI: 10.1073/pnas.1804992115 [Highlighted by Stefan Burén, Gema Ló pez-Torrejón, and Luis M. Rubio (2018) Extreme bioengineering tomeet the nitrogen challenge Proc Natl Acad Sci U S A. doi/10.1073/pnas.1812247115]
5. Zhu, M., Dai, X., Guo, W., Ge, Z., Yang, M., Wang, H., and Wang, Y.P.* (2017) Manipulating bacterial cell cycle and cell size by titrating the expression of ribonucleotide reductase. mBio 8: e01741-17..
6. Yang, J., Xie, X. Yang, M. Dixon, R.* and Wang, Y.P.* (2017) Modular electron transport chains from eukaryotic organelles function to support nitrogenase activity. Proc Natl Acad Sci U S A. 114: 3009-3011. doi:10.1073/pnas.1620058114 [Highlighted by Vicente, E.J. and Dean, D.R. Keeping the nitrogen-fixation dream alive. Proc Natl Acad Sci U S A. 2017, 114 (12): 3009-3011, doi:10.1073/pnas.1701560114. And by Good A. (2018) Toward nitrogen-fixing plants. Science 359 (6378): 869-870, DOI: 10.1126/science.aas8737]. It has been compiled by the Royal Society of Biology (UK) as one of The Big Biology Breakthroughs of 2017. https://www.rsb.org.uk/about-us/mysociety/158-biologist/features/1881-big-biology-breakthroughs-2017
7. Dai, X., Zhu, M., Warren, M., Balakrishnan, R., Patsalo, V., Okano, H., Williamson, J.R., Fredrick, K., Wang, Y.P.* Hwa, T.* Reduction of translating ribosomes enables Escherichia coli to maintain elongation rates during slow growth. Nature Microbiology 2016, 2:16231. doi: 10.1038/nmicrobiol.2016.231
8. Zhu, M., Dai, X.,* and Wang, Y.P.* Real time determination of bacterial in vivo ribosome translation elongation speed based on LacZ complementation system. Nucleic Acids Res. 2016, 44 (20): e155. doi: 10.1093/nar/gkw698.
9. Tian, Z.X*., Yi, X.X., Cho, A., O`Gara, F., and Wang, Y.P.* CpxR activates MexAB-OprM efflux pump expression and enhances antibiotic resistance in both laboratory and clinical nalB-type isolates of Pseudomonas aeruginosa. PLOS Pathogens 2016, 12(10):e1005932. doi: 10.1371/journal.ppat.1005932.
10. Wang, J., Yan, D., Dixon, R.*, and Wang, Y.P.* Deciphering the principles of bacterial nitrogen dietary preferences: a strategy for nutrient containment. mBio 2016, 7(4):e00792-16. doi:10.1128/mBio.00792-16.
11. Yang, Y., Darbari, V.C, Zhang, N., Lu, D., Glyde, R., Wang, Y.P., Winkelman, J., Gourse, R.L., Murakami, K.S., Buck, M., Zhang, X.*, Structures of the RNA polymerase-σ54 reveal new and conserved regulatory strategies. Science, 2015, 349: 882-885 doi: 10.1126/science.aab1478
12. Basan, M., Zhu, M., Dai, X., Warren, M., Sévin, D., Wang, Y.P., Hwa, T.*, Inflating bacterial cells by increased protein synthesis. Molecular Systems Biology, 2015, 11: 836.
13. Liang, J.L., Yong Nie, Y., Wang, M., Xiong, G., Wang, Y.P., Maser, E., and Wu, X.L.*, Regulation of alkane degradation pathway by a TetR family repressor via an autoregulation positive feedback mechanism in a Gram-positive Dietzia bacterium. Mol. Microbiol., 2015, 99(2):338-59. doi: 10.1111/mmi.13232.
14. Tian, C., Jinren Ni, J.*, Chang, F., Liu, S., Xu, N., Sun, W., Xie, Y., Guo, Y., Ma, Y., Yang, Z., Dang, C., Huang, Y., Tian, Z., and Wang, Y.P, Bio-Source of di-n-butyl phthalate production by filamentous fungi. Scientific Report, 2015, 6:19791. doi: 10.1038
15. Liu, J., Wen, J., Yang, J., Yang, Y., Wei, X., Zhang, X.* and Wang, Y.P.*, Mutational analysis of dimeric linkers in peri- and cytoplasmic domains of histidine kinase DctB reveal their functional roles in signal transduction, Open Biology, 2014, 4: 140023.
16. Zhang, Y., Jiang, F., Tian, Z., Huo, Y., Sun, Y., and Wang, Y.P.*, CRP-Cyclic AMP Dependent Inhibition of the Xylene-Responsive σ54-Promoter Pu in Escherichia coli, PLoS ONE 2014, 9(1): e86727.
17. Dai, X., Zhu, M., and Wang, Y.P.*, Circular permutation of E. coli EPSP synthase: increased inhibitor resistance, improved catalytic activity, and an indicator for protein fragment complementation , Chem. Commun., 2014, 50 (15): 1830 – 1832.
18. Yang, J., Xie, X., Wang, X., Dixon, R.*, and Wang, Y.P.*, Reconstruction and minimal gene requirement for the alternative iron-only nitrogenase system in Escherichia coli., Proc Natl Acad Sci U S A., 2014, 111(35): E3718-E3725 [Highlighted by Vicente, E.J. and Dean, D.R. Keeping the nitrogen-fixation dream alive. Proc Natl Acad Sci U S A. 2017, 114 (12): 3009-3011, doi:10.1073/pnas.1701560114]
19. Zhou, Y., Kolb, A., Busby, S.J.W., and Wang, Y.P.*, Spacing requirements for bacterial Class I transcrIption activation are set by promoter elements., Nucleic Acids Res., 2014, 42(14): 9209-16.
20. You, C., Okano, H., Hui, S., Zhang, Z., Kim, M., Gunderson, C.W., Wang, Y.P., Lenz, P., Yan, D., and Hwa, T.*, Coordination of bacterial proteome with metabolism by cAMP signalling, Nature, 2013, 500: 301-306
21. Wang, X., Yang, J., Chen, L., Cheng, Q., Dixon, R.*, and Wang, Y.P.*, Using Synthetic Biology to Distinguish and Overcome Regulatory and Functional Barriers Related to Nitrogen Fixation, PLoS ONE , 2013 , 8(7): e68677
22. Aogain, M.M., Mooij, M.J., McCarthy, R.R., Eimear Plower, E., Wang, Y.P., Tian, Z.X., Dobson, A.D.W., Morrissey, J.P. Claire Adams, C., and O`Gara, F.*, The non-classical ArsR-family repressor PyeR (PA4354) modulates biofilm formation in Pseudomonas aeruginosa, Microbiology , 2012, 158: 2598-2609
23. Jiang F, Tian Z.X., Wang Y.P.*, Characterization of ligand response properties of the CRP protein from Pseudomonas putida, Chinese Science Bulletin, 2012, 57: 3878-3885
24. Yan, H.Q., Chang, S.H., Tian, Z.X., Zhang, L., Sun, Y.C. Li, Y., Wang, J., and Wang, Y.P.*, Novel AroA from Pseudomonas putida Confers Tobacco Plant with High Tolerance to Glyphosate, PLoS ONE, 2011, 6:e19732
25. Li, Y., Sun, Y.C., Yan, H.Q., and Wang, Y.P.*, Alternative split sites for fragment complementation, and glyphosate function as extra ligand and stabilizer for the AroA enzyme complexes, Chinese Science Bulletin, 2011, 55: 1-7
26. Mooij M.J., O`Connor H.F., Tian Z.X., Wang Y.-P., Adams C., and O`Gara F.*, Antibiotic selection leads to inadvertent selection of nfxC-type phenotypic mutants in Pseudomonas aeruginosa, Environmental Microbiology Reports, 2010, 2: 461–464
27. Nan, B., Liu, X., Zhou, Y. Liu, J. Zhang L., Wen, J. Zhang, X., Su, X.D.* and Wang, Y.P.*, From signal perception to signal transduction: ligand-induced dimeric switch of DctB sensory domain in solution , Mol. Microbiol, 2010, 75: 1484–1494
28. Tian, Z.-X., MacAogáin, M., O`Connor, H.F., Fargier, E., Mooij, M.J., Adams, C., Wang, Y.-P., and O`Gara, F.*, MexT modulates virulence determinants in Pseudomonas aeruginosa independent of the MexEF-OprN efflux pump, Microb Pathog, 2009, 47: 237-241
29. Tian, Z.X., Fargier, E., MacAogáin, M., Adams, C., Wang, Y.P., and O`Gara, F.*, TranscrIptome profiling defines a novel regulon modulated by the LysR-type transcrIptional regulator MexT in Pseudomonas aeruginosa, Nucleic Acids Res, 2009, 37: 7546-7559.
30. Xiao, Y., Wigneshweraraj, S., Weinzierl, R., Wang, Y.P.*, and Buck, M , Construction and functional analyses of a comprehensive σ54 site-directed mutant library using alanine-cysteine mutagenesis, Nucleic Acids Res, 2009, 37: 4482-4497
31. Huo, Y.X., Zhang, Y.T., Xiao, Y., Zhang, X., Buck, M., Kolb, A., Wang, Y.P.*, IHF-binding sites inhibit DNA loop formation and transcrIption initiation, Nucleic Acids Res, 2009, 37: 3878-3886. [Highlighted in Faculty of 1000 by Prof. Jim Maher]
32. Zhou, Y.F., Nan, B, Nan, J., Ma, Q., Panjikar, S., Liang, Y.H., Wang, Y.P.*, and Su, X.D.*, C4-Dicarboxylates Sensing Mechanism Revealed by the Crystal Structures of DctB Sensor Domain , J. Mol. Biol , 2008 , 383: 49–61
33. Yan, Y., Yang, J., Dou, Y., Chen, M., Ping, S., Peng, J., Lu, W., Zhang, W., Yao, Z., Li, H., Liu, W., He, S., Geng, L., Zhang, X., Yang, F., Yu, H., Zhan, Y., Li, D., Lin, Z., Wang, Y., Elmerich, C., Lin, M., and Jin, Q., Nitrogen fixation island and rhizosphere competence traits in the genome of root-associated Pseudomonas stutzeri A1501, Proc Natl Acad Sci U S A , 2008 , 105: 7564-7569
34. Mao, X.J., Huo, Y.X., Buck, M., Kolb, A., and Wang Y.P.*, Interplay between CRP-cAMP and PII-Ntr systems forms novel regulatory network between carbon metabolism and nitrogen assimilation in Escherichia coli, Nucleic Acids Res, 2007, 35: 1432-40
35. Huo, Y.X., Tian, Z.X., Rappas, M., Wen, J., Chen, Y.C., You, C.H., Zhang, X.D., Buck, M., Wang, Y.P.* and Kolb, A., Protein-Induced-DNA-Bending clarifies the architectural organization of the σ54-dependent glnAp2 promoter. Mol. Microbiol., 2006, 59: 168-180. [Highlighted by Faculty of 1000 by Prof. Steven Busby]
36. Tian ZX, Li QS, Buck M, Kolb A and Wang Y.P.*, The CRP-cAMP complex and downregulation of the glnAp2 promoter provides a novel regulatory linkage between carbon metabolism and nitrogen assimilation in Escherichia coli , Mol. Microbiol., 2001, 41: 911-924.
37. Wang YP, Kolb A, Buck M, Wen J, O’Gara F and Buc H.*, CRP interacts with promoter-bound σ54 RNA polymerase and blocks transcrIptional activation of the dctA promoter, The EMBO J., 1998, 17: 786-796.
38. Wang, Y.P., Giblin, L., Boesten, B., and O’Gara, F.*, The Escherichia coli cAMP receptor protein (CRP) represses the Rhizobium meliloti dctA promoter in a cAMP dependent fashion. Mol. Microbiol., 1993, 8: 253-259.
39. Wang, Y.P., Birkenhead, K., Dobson, A., Boesten, B., and O’Gara, F.*, Sequences downstream from the transcrIptional start site are essential for microaerobic, but not symbiotic, expression of the Rhizobium meliloti nifHDK promoter. Mol. Microbiol., 1991, 5: 157-162.

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