CRISPR-Cas等微生物病毒免疫机制及其应用:  一方面，将围绕CRISPR-Cas、毒素-抗毒素、原核Argonaute等噬菌体免疫系统，通过解析其复杂多样的分子机制，系统认知微生物的噬菌体防御体系，并通过发掘其中蕴藏的特异性分子元件促进基因编辑等分子工具的创新。另一方面，致力于CRISPR等新一代基因编辑技术在微生物领域的应用和优化，面向重要工业底盘的系统性改造和临床多重耐药细菌的特异性消杀等需求，开发定制的、高效的基因编辑、基因驱动等技术。

硕士生、博士生

071007-遗传学
0710J3-生物信息学

噬菌体免疫，噬菌体治疗，基因编辑，微生物群编辑

2008-09--2014-07   中国科学院大学   理学博士
2004-09--2008-07   山东大学   理学学士

博士研究生

理学博士

   

2022-10~现在, 中国科学院微生物研究所, 研究员
2020-12~2022-10,中国科学院微生物研究所, 项目研究员/青年课题组长
2017-09~2020-12,中国科学院微生物研究所, 副研究员
2016-11~2017-08,中国科学院微生物研究所, 助理研究员
2014-11~2016-10,中国科学院北京基因组研究所, 博士后

　　2014年中国科学院院长优秀奖 

　　2015年度中国科学院百篇优秀博士学位论文 

　　2017年入选中国科协青年人才托举工程 

　　2020年入选中国科学院青年创新促进会会员

（ 1 ） 一种联用CRISPR和毒素-抗毒素精准高效消杀耐药细菌, 发明专利, 2022, 第 1 作者, 专利号: 202210947272.7

（ 2 ） 广谱识别PAM序列的FnCpf1突变体及其应用, 发明专利, 2020, 第 2 作者, 专利号: CN112111471A

   

[1] Rui Wang, Xian Shu, Huiwei Zhao, Qiong Xue, Chao Liu, Aici Wu, Feiyue Cheng, Lingyun Wang, Yihan Zhang, Jie Feng, Nannan Wu, Ming Li. Associate toxin-antitoxin with CRISPR-Cas to kill multidrug-resistant pathogens. NATURE COMMUNICATIONS[J]. 2023, 14(1): 1-13, https://doaj.org/article/9af6f50038e3452486b995a0d6ccf7c5.
[2] Cheng, Feiyue, Wu, Aici, Liu, Chao, Cao, Xifeng, Wang, Rui, Shu, Xian, Wang, Lingyun, Zhang, Yihan, Xiang, Hua, Li, Ming. The toxin-antitoxin RNA guards of CRISPR-Cas evolved high specificity through repeat degeneration. NUCLEIC ACIDS RESEARCH[J]. 2022, 50(16): 9442-9452, http://dx.doi.org/10.1093/nar/gkac712.
[3] Chen, Zehua, Sun, Jinyuan, Guan, Ying, Li, Ming, Lou, Chunbo, Wu, Bian. Engineered DNase-inactive Cpf1 variants to improve targeting scope for base editing in E. coli. SYNTHETIC AND SYSTEMS BIOTECHNOLOGY[J]. 2021, 6(4): 326-334, http://dx.doi.org/10.1016/j.synbio.2021.09.002.
[4] Xu, Zeling, Li, Yanran, Li, Ming, Xiang, Hua, Yan, Aixin. Harnessing the type ICRISPR-Cassystems for genome editing in prokaryotes. ENVIRONMENTAL MICROBIOLOGY[J]. 2021, 23(2): 542-558, https://www.webofscience.com/wos/woscc/full-record/WOS:000543749700001.
[5] Li, Ming, Gong, Luyao, Cheng, Feiyue, Yu, Haiying, Zhao, Dahe, Wang, Rui, Wang, Tian, Zhang, Shengjie, Zhou, Jian, Shmakov, Sergey A, Koonin, Eugene, V, Xiang, Hua. Toxin-antitoxin RNA pairs safeguard CRISPR-Cas systems. SCIENCE[J]. 2021, 372(6541): 481-+, http://dx.doi.org/10.1126/science.abe5601.
[6] Cheng, Feiyue, Wang, Rui, Yu, Haiying, Liu, Chao, Yang, Jun, Xiang, Hua, Li, Ming. Divergent degeneration of creA antitoxin genes from minimal CRISPRs and the convergent strategy of tRNA-sequestering CreT toxins. NUCLEIC ACIDS RESEARCH[J]. 2021, 49(18): 10677-10688, http://dx.doi.org/10.1093/nar/gkab821.
[7] Zhao, Dahe, Zhang, Shengjie, Xue, Qiong, Chen, Junyu, Zhou, Jian, Cheng, Feiyue, Li, Ming, Zhu, Yaxin, Yu, Haiying, Hu, Songnian, Zheng, Yanning, Liu, Shuangjiang, Xiang, Hua. Abundant Taxa and Favorable Pathways in the Microbiome of Soda-Saline Lakes in Inner Mongolia. FRONTIERS IN MICROBIOLOGY[J]. 2020, 11: https://doaj.org/article/57a04408b4814c8f99efb62ef2258896.
[8] Kumar, Sumit, Zhou, Jian, Li, Ming, Xiang, Hua, Zhao, Dahe. Insights into the metabolism pathway and functional genes of long-chain aliphatic alkane degradation in haloarchaea. EXTREMOPHILES[J]. 2020, 24(4): 475-483, http://dx.doi.org/10.1007/s00792-020-01167-z.
[9] Gong, Luyao, Li, Ming, Cheng, Feiyue, Zhao, Dahe, Chen, Yihua, Xiang, Hua. Primed adaptation tolerates extensive structural and size variations of the CRISPR RNA guide in Haloarcula hispanica. NUCLEIC ACIDS RESEARCH[J]. 2019, 47(11): 5880-5891, https://www.webofscience.com/wos/woscc/full-record/WOS:000475702000039.
[10] Xu, Zeling, Li, Ming, Li, Yanran, Cao, Huiluo, Miao, Lu, Xu, Zhaochao, Higuchi, Yusuke, Yamasaki, Seiji, Nishino, Kunihiko, Woo, Patrick C Y, Xiang, Hua, Yan, Aixin. Native CRISPR-Cas-Mediated Genome Editing Enables Dissecting and Sensitizing Clinical Multidrug-Resistant P. aeruginosa. CELLREPORTS[J]. 2019, 29(6): 1707-+, http://dx.doi.org/10.1016/j.celrep.2019.10.006.
[11] 向华. Xu Z, Li M, Li Y, Cao H, Miao L, Xu Z, Higuchi Y, Yamasaki S, Nishino K, Woo PCY, Xiang H, Yan A. Native CRISPR-Cas-Mediated Genome Editing Enables Dissecting and Sensitizing Clinical Multidrug-Resistant P. aeruginosa.. Cell Rep.29(6):1707-1717. 2019, [12] 东秀珠, 李猛, 向华, 徐俊, 王风平, 申玉龙, 张臻峰, 韩静, 李洁, 李明, 黄力. 探秘生命的第三种形式--我国古菌研究之回顾与展望. 中国科学:生命科学[J]. 2019, 49(11): 1520-1542, https://www.sciengine.com/doi/10.1360/SSV-2019-0138.
[13] 李明, 程飞跃, 龚路遥, 向华. 微生物新型防御系统的系统性发现与展望. 遗传[J]. 2018, 40(4): 259-265,  http://dx.doi.org/10.16288/j.yczz.18-075.
[14] 向华. Cheng F, Gong L, Zhao D, Yang H, Zhou J, Li M, Xiang H*, 2017, Harnessing the native type I-B CRISPR-Cas for genome editing in a polyploid archaeon.. J Genet Genomics, 44: 541-548. 2017, [15] Zhao, Dahe, Yang, Haibo, Chen, Junyu, Cheng, Feiyue, Kumar, Sumit, Han, Jing, Li, Ming, Zhou, Jian, Xiang, Hua. Development of the first gene expression system for Salinicoccus strains with potential application in bioremediation of hypersaline wastewaters. APPLIED MICROBIOLOGY AND BIOTECHNOLOGY[J]. 2017, 101(19): 7249-7258, http://dx.doi.org/10.1007/s00253-017-8428-9.
[16] Zhao, Dahe, Kumar, Sumit, Zhou, Jian, Wang, Rui, Li, Ming, Xiang, Hua. Isolation and complete genome sequence of Halorientalis hydrocarbonoclasticus sp nov., a hydrocarbon-degrading haloarchaeon. EXTREMOPHILES[J]. 2017, 21(6): 1081-1090, http://dx.doi.org/10.1007/s00792-017-0968-5.
[17] Cheng, Feiyue, Gong, Luyao, Zhao, Dahe, Yang, Haibo, Zhou, Jian, Li, Ming, Xiang, Hua. Harnessing the native type I-B CRISPR-Cas for genome editing in a polyploid archaeon. JOURNAL OF GENETICS AND GENOMICS[J]. 2017, 44(11): 541-548, http://dx.doi.org/10.1016/j.jgg.2017.09.010.
[18] Li, Ming, Gong, Luyao, Zhao, Dahe, Zhou, Jian, Xiang, Hua. The spacer size of I-B CRISPR is modulated by the terminal sequence of the protospacer. NUCLEIC ACIDS RESEARCH[J]. 2017, 45(8): 4642-4654, https://www.webofscience.com/wos/woscc/full-record/WOS:000400578600037.
[19] Wang, Rui, Li, Ming, Gong, Luyao, Hu, Songnian, Xiang, Hua. DNA motifs determining the accuracy of repeat duplication during CRISPR adaptation in Haloarcula hispanica. NUCLEIC ACIDS RESEARCH[J]. 2016, 44(9): 4266-4277, http://dx.doi.org/10.1093/nar/gkw260.
[20] Li, Ming, Wang, Rui, Xiang, Hua. Haloarcula hispanica CRISPR authenticates PAM of a target sequence to prime discriminative adaptation. NUCLEIC ACIDS RESEARCH[J]. 2014, 42(11): 7226-7235, https://www.webofscience.com/wos/woscc/full-record/WOS:000338769400042.
[21] Cai, Lei, Cai, Shuangfeng, Zhao, Dahe, Wu, Jinhua, Wang, Lei, Liu, Xiaoqing, Li, Ming, Hou, Jing, Zhou, Jian, Liu, Jingfang, Han, Jing, Xiang, Hua. Analysis of the Transcriptional Regulator GlpR, Promoter Elements, and Posttranscriptional Processing Involved in Fructose-Induced Activation of the Phosphoenolpyruvate-Dependent Sugar Phosphotransferase System in Haloferax mediterranei. APPLIED AND ENVIRONMENTAL MICROBIOLOGY[J]. 2014, 80(4): 1430-1440, https://www.webofscience.com/wos/woscc/full-record/WOS:000331625100023.
[22] Li, Ming, Wang, Rui, Zhao, Dahe, Xiang, Hua. Adaptation of the Haloarcula hispanica CRISPR-Cas system to a purified virus strictly requires a priming process. NUCLEIC ACIDS RESEARCH[J]. 2014, 42(4): 2483-2492, https://www.webofscience.com/wos/woscc/full-record/WOS:000332381000040.
[23] Han, Jing, Hou, Jing, Zhang, Fan, Ai, Guomin, Li, Ming, Cai, Shuangfeng, Liu, Hailong, Wang, Lei, Wang, Zejian, Zhang, Siliang, Cai, Lei, Zhao, Dahe, Zhou, Jian, Xiang, Hua. Multiple Propionyl Coenzyme A-Supplying Pathways for Production of the Bioplastic Poly(3-Hydroxybutyrate-co-3-Hydroxyvalerate) in Haloferax mediterranei. APPLIED AND ENVIRONMENTAL MICROBIOLOGY[J]. 2013, 79(9): 2922-2931, https://www.webofscience.com/wos/woscc/full-record/WOS:000317474800009.
[24] Li, Ming, Liu, Hailong, Han, Jing, Liu, Jingfang, Wang, Rui, Zhao, Dahe, Zhou, Jian, Xiang, Hua. Characterization of CRISPR RNA Biogenesis and Cas6 Cleavage-Mediated Inhibition of a Provirus in the Haloarchaeon Haloferax mediterranei. JOURNAL OF BACTERIOLOGY[J]. 2013, 195(4): 867-875, https://www.webofscience.com/wos/woscc/full-record/WOS:000316961200024.
[25] Liu, Hailong, Luo, Yuanming, Han, Jing, Wu, Jinhua, Wu, Zhenfang, Feng, Deqin, Cai, Shuangfeng, Li, Ming, Liu, Jingfang, Zhou, Jian, Xiang, Hua. Proteome Reference Map of Haloarcula hispanica and Comparative Proteomic and Transcriptomic Analysis of Polyhydroxyalkanoate Biosynthesis under Genetic and Environmental Perturbations. JOURNAL OF PROTEOME RESEARCH[J]. 2013, 12(3): 1300-1315, https://www.webofscience.com/wos/woscc/full-record/WOS:000315708000022.
[26] Zhao, Dahe, Cai, Lei, Wu, Jinhua, Li, Ming, Liu, Hailong, Han, Jing, Zhou, Jian, Xiang, Hua. Improving polyhydroxyalkanoate production by knocking out the genes involved in exopolysaccharide biosynthesis in Haloferax mediterranei. APPLIED MICROBIOLOGY AND BIOTECHNOLOGY[J]. 2013, 97(7): 3027-3036, https://www.webofscience.com/wos/woscc/full-record/WOS:000316481800024.
[27] 向华. Li M, Liu H, Han J, Liu J, Wang R, Zhao D, Zhou J, Xiang H*. Characterization of CRISPR RNA biogenesis and Cas6-cleavage mediated inhibition of a provirus in the haloarchaeon Haloferax mediterranei.. Journal of Bacteriology, 195(4):867-75. 2013, [28] Han, Jing, Zhang, Fan, Hou, Jing, Liu, Xiaoqing, Li, Ming, Liu, Hailong, Cai, Lei, Zhang, Bing, Chen, Yaping, Zhou, Jian, Hu, Songnian, Xiang, Hua. Complete Genome Sequence of the Metabolically Versatile Halophilic Archaeon Haloferax mediterranei, a Poly(3-Hydroxybutyrate-co-3-Hydroxyvalerate) Producer. JOURNAL OF BACTERIOLOGY[J]. 2012, 194(16): 4463-4464, https://www.webofscience.com/wos/woscc/full-record/WOS:000307198100049.
[29] Liu, Hailong, Wu, Zhenfang, Li, Ming, Zhang, Fan, Zheng, Huajun, Han, Jing, Liu, Jingfang, Zhou, Jian, Wang, Shengyue, Xiang, Hua. Complete Genome Sequence of Haloarcula hispanica, a Model Haloarchaeon for Studying Genetics, Metabolism, and Virus-Host Interaction. JOURNAL OF BACTERIOLOGY[J]. 2011, 193(21): 6086-6087, https://www.webofscience.com/wos/woscc/full-record/WOS:000296153400021.
[30] Kaixin Du, Luyao Gong, Ming Li, Haiying Yu, Hua Xiang. Reprogramming the endogenous type I CRISPR‐Cas system for simultaneous gene regulation and editing in Haloarcula hispanica. MLIFE. 1: https://www.sciengine.com/doi/10.1002/mlf2.12010.

   

（ 1 ） CRISPR-Cas与一种新型毒素-抗毒素系统的偶联机制研究, 负责人, 国家任务, 2018-01--2021-12
（ 2 ） 偶联核酸酶的常温pAgo系统的功能机制和分子应用研究, 负责人, 国家任务, 2020-01--2023-12
（ 3 ） 微生物新型核酸免疫机制的发掘, 负责人, 国家任务, 2019-01--2020-12
（ 4 ） 微生物来源核酸靶向元件的发掘和优化, 负责人, 国家任务, 2019-01--2020-12
（ 5 ） 中国科学院青年创新促进会, 负责人, 中国科学院计划, 2020-01--2023-12
（ 6 ） 中国科协青年人才托举工程, 负责人, 国家任务, 2017-10--2020-10
（ 7 ） 微生物的病毒防御机制及应用, 负责人, 国家任务, 2021-01--2023-12
（ 8 ） CRISPR护卫RNA的系统性认知及其分子应用开发, 负责人, 国家任务, 2022-01--2024-12

（1）Defense，anti-defense and anti-anti-defense between bacteria and phages   2021第四届超级细菌感染与噬菌体防治高峰论坛   2021-07-18
（2）微生物基因组中的“暗物质”   第八届全国微生物基因组学学术研讨会   李明   2021-07-09
（3）CRISPR适应性免疫机制及其基因编辑应用   2020年中国微生物学会学术年会   李明   2020-10-23
（4）微生物适应性免疫与新型毒素-抗毒素系统的功能偶联   2019年全国微生物学青年学者学术研讨会   2019-09-20
（5）The significance, effectiveness and robustness of priming during CRISPR adaptation in Haloarcula hispanica   CRISPR 2019   2019-06-16
（6）CRISPR-Cas系统适应性和稳定性的分子基础   2017年中国微生物学会学术年会   2017-10-20

现指导学生

舒宪  博士研究生  071007-遗传学  

伍蔼慈  硕士研究生  0710J3-生物信息学  

曹夕凤  硕士研究生  071007-遗传学  

刘超  博士研究生  071007-遗传学