1）  共生微生物及其与宿主的共生机制

肠道共生微生物不仅对食物的消化吸收起着重要的作用，而且对宿主的病毒防御、免疫调控等也起着举足轻重的作用，本课题组利用深海海试或深渊航次获取的样品，对南海1000米大王具足虫、马里亚纳海沟6000米深渊海参，以及马里亚纳海沟狮子鱼、万米钩虾进行肠道共生微生物的研究。研究结果发现，柔壁菌门薄膜菌钢的微生物如支原体、螺原体、脲原菌与深海生物形成共生，并成为优势共生菌。这些共生微生物为宿主提供机体所必需的营养物质如维生素，帮助宿主进行能量获取如纤维素的降解，为宿主提供免疫机制如应用CRIPR机制抵制病毒的入侵等。而这些微生物在大多数情况下是陆生生物或人类的病原菌。已发表文章《Applied & Environmental Microbiology》（IF3.7；top期刊；JCR：2区；）、《Environmental Microbiology》（IF5.0；top 期刊；JCR：1区）、《Nucleic Acids Research》(IF 11.6; top 期刊；JCR：1区)、《Frontiers in Microbiology》（IF4.3； JCR： 1区）、《Deep Sea Research Part I: Oceanagraphic Research Papers》（IF2.8； JCR：1区）等。文章一经发表，立即得到美国微生物协会两位主席Moselio Schaechter教授和哈佛大学Roberto Kolter教授迅速做出评价，认为该文提供了深海生物与柔壁门共生菌共同应对深海极端环境的确实证据（该菌习惯上被认为只是人畜病原菌）。

2）  深海生物特有的调控通路及代谢通路

深海生物为适应深海的高压、无光、低温及寡营养的极端环境，不仅在外表形态如嘴巴变大，牙齿异常锋利外，在分子水平也有着不同于生存于浅海环境生物的代谢及调控特征。本课题组发现万米深渊除Hirondellea gigas外，另一个优势物种Halice sp. MT2017，其分化时间分别在约58Mya和109Mya，而马里亚纳海沟形成时间是约30Mya，提示深渊物种从浅海物种演化而来。应用这两种万米钩虾，与浅海钩虾比较，研究发现万米钩虾的骨架蛋白扩张及高度磷酸化，包括微丝蛋白、微管蛋白、中间丝蛋白及调控骨架聚合与解离的骨架结合蛋白。细胞骨架在高压情况下会塌陷，从而影响细胞的形态、信息传导、细胞分裂等细胞生命活动。骨架蛋白通对磷酸化对骨架的聚合解聚等活动进行调节；可变剪切在真核生物体内广泛存在，其中有95%的基因都存在可变剪切现象。可变剪切导致了转录本和蛋白质结构与功能的多态性，是一种重要的转录调控机制。不同的剪切方式使得同一个基因可以产生多个不同的成熟mRNA, 最终产生不同的蛋白质。万米钩虾转录后剪切相关基因与浅海钩虾相比得到正选择；同时发现深渊钩虾线粒体蛋白的非极性氨基酸的比例明显高于源于浅海的钩虾。本研究分别从DNA水平、转录水平及蛋白后修饰水平提示深渊钩环境适应的分子机制。部分研究成果发表在《Scientific Reports》（IF5.02， JCR 1区）、《International Journal of Biological Macromolecules》（IF 4.78， JCR 1区）等。

3）  源于深海酶类的研究

深海的环境特殊，必然存在着具有特别活性或活性特异的酶类。本课题组从南中国海1000米捕获的大王具足虫的共生菌里克隆并表达了唾液酸裂解酶。唾液酸裂解酶具有逆向合成唾液酸的功能。唾液酸是神经节苷脂的传递递质，是大脑的组成部分，是婴幼儿奶粉的主要添加剂之一。目前的唾液酸主要靠工业发酵纯化获得。本项目研究发现源于深海的唾液酸裂解酶的活性是目前报导的所有唾液酸裂解酶的4-10倍。并且具有较强的pH 值适应范围。为工业用酶提供了新选择。研究成果已发表在《Marine Drugs》（IF：4.4;JCR: 1区）。除此之外，本课题组从热虾中克隆并表达了多种抗菌肽，对多种耐药菌株具有显著的抑菌效果。

4）深海生物捕获装置的研发

目前我国的深海特别是深渊生物的研究与陆生生物的研究相比， 相差较远， 原因之一便是生物的获取困难，为此，为揽瓷器活，先做金刚钻。本课题组联合本所工程人员，研制了宏生物防逃逸诱捕器，保温宏生物诱捕器以及配合载人深潜器机械手使用的负压吸引器。这些装置均已在多个航次中成功使用。

具有组学、分子生物化学、生物信息分析等研究背景的学生优先。

070703-海洋生物学

极端环境下生物的适应机制
深海生物的共生
深海酶学研究

2003-09--2007-09   香港科技大学   博士
2000-09--2003-09   北京大学   硕士
1995-09--2000-09   北京大学   本科

博士

博士研究生

   

2013-09~现在, 中国科学院深海科学与工程研究所, 研究员
2007-09~2013-09,香港科技大学, 博士后

海洋生物肠道共生微生物结构及功能的初步解析

（1） 南海“人才系列” 南海名家, 省级, 2019
（2） 海南省领军人才, , 省级, 2019
（3） 国家自然科学奖, 二等奖, 国家级, 2016
（4） 博士后研究基金, , 研究所（学校）, 2008

[1] 贺丽生, 郭璐璐, 王少露, 朱方超. 抗菌肽及其制备方法和应用. CN: CN113880931A, 2022-01-04.
[2] 李文莉, 王勇, 位站飞, 李俊, 高兆明, 贺丽生. 用于深海微生物原位细胞裂解的组合物、试剂、试剂盒及应用. CN: CN111534509A, 2020-08-14.
[3] 李俊, 辛永智, 蔡笃思, 李文莉, 王勇, 王绥学, 王瑞星, 陈俊, 高兆明, 贺丽生. 一种全海深微生物核酸原位提取装置. CN: CN209854124U, 2019-12-27.
[4] 李俊, 辛永智, 蔡笃思, 李文莉, 王勇, 王绥学, 王瑞星, 陈俊, 高兆明, 贺丽生. 一种全海深微生物核酸原位提取装置. CN: CN109852532A, 2019-06-07.
[5] 程项雨, 贺丽生. 源于马里亚纳和雅浦深渊钩虾肠道共生菌的基因. CN: CN109576382A, 2019-04-05.
[6] 李俊元, 贺丽生, 闫国永. 源于一种深渊新物种的线粒体基因组序列. CN: CN108300720A, 2018-07-20.
[7] 王少露, 贺丽生, 王勇. 唾液酸酶基因重组表达载体及其构建方法，唾液酸酶及其制备方法. CN: CN106906236A, 2017-06-30.
[8] 李俊, 王勇, 蔡笃思, 高兆明, 贺丽生, 张艾群, 高怀宁. 一种应用于全海深的微生物原位自动化富集固定装置. CN: CN205241694U, 2016-05-18.
[9] 李俊, 贺丽生, 张艾群, 王勇, 蔡笃思. 一种深海底栖生物防逃逸诱捕器. CN: CN205196755U, 2016-05-04.
[10] 李俊, 贺丽生, 张艾群, 王勇, 蔡笃思. 一种深海底栖生物防逃逸诱捕器. CN: CN105409894A, 2016-03-23.
[11] 李俊, 王勇, 蔡笃思, 高兆明, 贺丽生, 张艾群, 高怀宁. 一种应用于全海深的微生物原位自动化富集固定装置及方法. CN: CN105420097A, 2016-03-23.

   

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[18] Kou, Qi, Meland, Kenneth, Li, Xinzheng, He, Lisheng, Wang, Yong. "Unicorn from Hades", a new genus of Mysidae (Malacostraca: Mysida) from the Mariana Trench, with a systematic analysis of the deep-sea mysids. MOLECULAR PHYLOGENETICS AND EVOLUTION[J]. 2020, 第 4 作者143: http://dx.doi.org/10.1016/j.ympev.2019.106666.
[19] FangChao Zhu, Jin Sun, GuoYong Yan, JiaoMei Huang, Chong Chen, LiSheng He. Insights into the strategy of micro-environmental adaptation: Transcriptomic analysis of two alvinocaridid shrimps at a hydrothermal vent.. PLOS ONE[J]. 2020, 第 6 作者  通讯作者  15(1): 16, https://doaj.org/article/d4001eca13874fbf94051898dcef5554.
[20] Yan, Guoyong, Sun, Jin, Wang, Zishuai, Qian, PeiYuan, He, Lisheng. Insights into the Synthesis, Secretion and Curing of Barnacle Cyprid Adhesive via Transcriptomic and Proteomic Analyses of the Cement Gland. MARINE DRUGS[J]. 2020, 第 5 作者  通讯作者  18(4): https://doaj.org/article/7dae0f76251946c19993458d6385b834.
[21] Lian, ChunAng, Li, JunYuan, Zhu, FangChao, Li, Jun, He, LiSheng. The complete mitochondrial genome of a new deep-sea hagfish Eptatretus sp. Nan-Hai (Myxinidae: Eptatretus) from the South China Sea. MITOCHONDRIAL DNA PART B-RESOURCES[J]. 2020, 第 5 作者  通讯作者  5(1): 619-620, https://www.webofscience.com/wos/woscc/full-record/WOS:000507596700001.
[22] Li, Junyuan, Liao, Yanwen, Li, Jun, He, Lisheng. The complete mitochondrial genome of the deep-sea amphipod Eurythenes magellanicus (Crustacea: Amphipoda: Lysianassidae). MITOCHONDRIAL DNA PART B-RESOURCES[J]. 2020, 第 4 作者  通讯作者  5(1): 337-339, http://apps.webofknowledge.com/CitedFullRecord.do?product=UA&colName=WOS&SID=5CCFccWmJJRAuMzNPjj&search_mode=CitedFullRecord&isickref=WOS:000589839400004.
[23] Gong, Lin, Li, Xinzheng, Xiao, Ning, He, Lisheng, Zhang, Haibin, Wang, Yong. Rediscovery of the abyssal speciesPeniagone leanderPawson and Foell, 1986 (Holothuroidea: Elasipodida: Elpidiidae): the first record from the Mariana Trench area. JOURNAL OF OCEANOLOGY AND LIMNOLOGY[J]. 2020, 第 4 作者38(4): 1319-1327, http://lib.cqvip.com/Qikan/Article/Detail?id=7102292182.
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[37] Li, Junyuan, Guo, Donghui, Wu, Pengcheng, He, Lisheng. Ontogeny reversal and phylogenetic analysis of Turritopsis sp.5 (Cnidaria, Hydrozoa, Oceaniidae), a possible new species endemic to Xiamen, China. PEERJ[J]. 2018, 第 4 作者  通讯作者  6: http://ir.idsse.ac.cn/handle/183446/5919.
[38] He, LiSheng, Zhang, Gen, Wang, Yong, Yan, GuoYong, Qian, PeiYuan. Toward understanding barnacle cementing by characterization of one cement protein-100kDa in Amphibalanus amphitrite. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS[J]. 2018, 第 1 作者495(1): 969-975, http://ir.idsse.ac.cn/handle/183446/5926.
[39] Wang, Yong, Zhu, FangChao, He, LiSheng, Danchin, Antoine. Unique tRNA gene profile suggests paucity of nucleotide modifications in anticodons of a deep-sea symbiotic Spiroplasma. NUCLEIC ACIDS RESEARCH[J]. 2018, 第 3 作者46(5): 2197-2203, http://ir.idsse.ac.cn/handle/183446/5927.
[40] He, LiSheng, Zhang, PeiWei, Huang, JiaoMei, Zhu, FangChao, Danchin, Antoine, Wang, Yong. The Enigmatic Genome of an Obligate Ancient Spiroplasma Symbiont in a Hadal Holothurian. APPLIED AND ENVIRONMENTAL MICROBIOLOGY[J]. 2018, 第 1 作者84(1): http://ir.idsse.ac.cn/handle/183446/5203.
[41] Wang, Shaolu, Li, Yunliang, Han, Zhuang, Chen, Xi, Chen, Qijia, Wang, Yong, He, Lisheng. Molecular Characterization of a Novel N-Acetylneuraminate Lyase from a Deep-Sea Symbiotic Mycoplasma. MARINE DRUGS[J]. 2018, 第 7 作者  通讯作者  16(3): http://ir.idsse.ac.cn/handle/183446/5966.
[42] He Lisheng. Ontogeny reversal and phylogenetic analysis of Turritopsis sp.5 (Cnidaria, Hydrozoa, Oceaniidae), a species endemic to Xiamen, China.. PEERJ. 2018, 第 1 作者  通讯作者  
[43] Kou, Qi, Li, Xinzheng, He, Lisheng, Wang, Yong. Rediscovery of the hadal species Amblyops magnus Birstein & Tchindonova, 1958 (Crustacea: Mysida: Mysidae): first record from the Mariana Trench. ZOOTAXA[J]. 2018, 第 3 作者4402(1): 42-52, http://ir.idsse.ac.cn/handle/183446/5932.
[44] Lan, Yi, Sun, Jin, Tian, Renmao, Bartlett, Douglas H, Li, Runsheng, Wong, Yue Him, Zhang, Weipeng, Qiu, JianWen, Xu, Ting, He, LiSheng, Tabata, Harry G, Qian, PeiYuan. Molecular adaptation in the world's deepest-living animal: Insights from transcriptome sequencing of the hadal amphipod Hirondellea gigas. MOLECULAR ECOLOGY[J]. 2017, 第 10 作者26(14): 3732-3743, http://ir.idsse.ac.cn/handle/183446/3962.
[45] Kou, Qi, Chen, Jun, Li, Xinzheng, He, Lisheng, Wang, Yong. New species of the giant deep-sea isopod genus Bathynomus (Crustacea, Isopoda, Cirolanidae) from Hainan Island, South China Sea. INTEGRATIVE ZOOLOGY[J]. 2017, 第 4 作者12(4): 283-291, http://ir.qdio.ac.cn/handle/337002/137031.
[46] Shen, Yanjun, Kou, Qi, Zhong, Zaixuan, Li, Xinzheng, He, Lisheng, He, Shunping, Gan, Xiaoni. The first complete mitogenome of the South China deep-sea giant isopod Bathynomus sp (Crustacea: Isopoda: Cirolanidae) allows insights into the early mitogenomic evolution of isopods. ECOLOGY AND EVOLUTION[J]. 2017, 第 5 作者7(6): 1869-1881, http://dx.doi.org/10.1002/ece3.2737.
[47] Yan, Guoyong, Zhang, Gen, Huang, Jiaomei, Lan, Yi, Sun, Jin, Zeng, Cong, Wang, Yong, Qian, PeiYuan, He, Lisheng. Comparative Transcriptomic Analysis Reveals Candidate Genes and Pathways Involved in Larval Settlement of the Barnacle Megabalanus volcano. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES[J]. 2017, 第 9 作者  通讯作者  18(11): http://ir.idsse.ac.cn/handle/183446/5270.
[48] 寇琦. A new species of the giant deep-sea isopod genus Bathynomus A. Milne Edwards, 1879 (Crustacea, Isopoda, Cirolanidae) from Hainan Island, South China Sea. Integrative Zoology. 2017, 
[49] He Lisheng. The enigmatic genome of an obligate ancient Spiroplasma symbiont in a hadal holothurian.. Applied and environmental microbiology. 2017, 第 1 作者
[50] Wang Yong, Gao Zhaoming, Xu Ying, Li Guangyu, He Lisheng, Qian Peiyuan. An evaluation of multiple annealing and looping based genome amplification using a synthetic bacterial community. ACTA OCEANOLOGICA SINICA[J]. 2016, 第 5 作者35(2): 131-136, http://lib.cqvip.com/Qikan/Article/Detail?id=667983978.
[51] Wong, Yue Him, Yu, Li, Zhang, Gen, He, LiSheng, Qian, PeiYuan. In Silico Prediction of Neuropeptides/Peptide Hormone Transcripts in the Cheilostome Bryozoan Bugula neritina. PLOS ONE[J]. 2016, 第 4 作者11(8): http://ir.idsse.ac.cn/handle/183446/1608.
[52] Wang, Yong, Huang, JiaoMei, Wang, ShaoLu, Gao, ZhaoMing, Zhang, AiQun, Danchin, Antoine, He, LiSheng. Genomic characterization of symbiotic mycoplasmas from the stomach of deep-sea isopod bathynomus sp. ENVIRONMENTAL MICROBIOLOGY[J]. 2016, 第 7 作者  通讯作者  18(8): 2646-2659, https://www.webofscience.com/wos/woscc/full-record/WOS:000383388800032.
[53] Zhang, Gen, Yang, XiaoXue, Leung, Pok Man, He, LiSheng, Chan, Tat Yin, Yan, GuoYong, Zhang, Yu, Sun, Jin, Xu, Ying, Qian, PeiYuan. Secretory locations of SIPC in Amphibalanus amphitrite cyprids and a novel function of SIPC in biomineralization. SCIENTIFIC REPORTS[J]. 2016, 第 4 作者6: http://ir.idsse.ac.cn/handle/183446/1597.
[54] Zhang, Gen, Yan, GuoYong, Yang, XiaoXue, Wong, YueHim, Sun, Jin, Zhang, Yu, He, LiSheng, Xu, Ying, Qian, PeiYuan. Characterization of Arginine Kinase in the Barnacle Amphibalanus Amphitrite and Its Role in the Larval Settlement. JOURNAL OF EXPERIMENTAL ZOOLOGY PART B-MOLECULAR AND DEVELOPMENTAL EVOLUTION[J]. 2016, 第 7 作者326(4): 237-249, http://ir.idsse.ac.cn/handle/183446/1579.
[55] Wang Yong. Wang Y, Huang JM, Wang SL, Gao ZM, Zhang AQ, Danchin A*, He LS*. 2016. Genomic characterization of symbiotic mycoplasmas from the stomach of deep-sea isopod bathynomus sp. 18(8): 13411. Environmental Microbiology,. 2016, 
[56] Gen Zhang, LiSheng He, Yue Him Wong, Ying Xu, Yu Zhang, PeiYuan Qian. p38 MAPK regulates PKAα and CUB-serine protease in Amphibalanus amphitrite cyprids. SCIENTIFIC REPORTS. 2015, 第 2 作者5: 
[57] Wong, Yue Him, Sun, Jin, He, Li Sheng, Chen, Lian Guo, Qiu, JianWen, Qian, PeiYuan. High-throughput transcriptome sequencing of the cold seep mussel Bathymodiolus platifrons. SCIENTIFIC REPORTS[J]. 2015, 第 3 作者5: http://dx.doi.org/10.1038/srep16597.
[58] Zhang, Gen, He, LiSheng, Wong, Yue Him, Yu, Li, Qian, PeiYuan. siRNA transfection in larvae of the barnacle Amphibalanus amphitrite. JOURNAL OF EXPERIMENTAL BIOLOGY[J]. 2015, 第 2 作者218(16): 2505-2509, http://ir.idsse.ac.cn/handle/183446/1213.
[59] Zhang, Gen, Wong, YueHim, Zhang, Yu, He, LiSheng, Xu, Ying, Qian, PeiYuan. Nitric oxide inhibits larval settlement in Amphibalanus amphitrite cyprids by repressing muscle locomotion and molting. PROTEOMICS[J]. 2015, 第 4 作者15(22): 3854-3864, http://ir.idsse.ac.cn/handle/183446/1343.
[60] Zhang, Gen, He, Lisheng, Wong, YueHim, Xu, Ying, Zhang, Yu, Qian, Peiyuan. Chemical Component and Proteomic Study of the Amphibalanus (= Balanus) amphitrite Shell. PLOS ONE[J]. 2015, 第 2 作者10(7): http://ir.idsse.ac.cn/handle/183446/1212.
[61] Zhang, Gen, He, LiSheng, Wong, Yue Him, Xu, Ying, Zhang, Yu, Qian, PeiYuan. p38 MAPK regulates PKA alpha and CUB-serine protease in Amphibalanus amphitrite cyprids. SCIENTIFICREPORTS[J]. 2015, 第 2 作者5(1): http://124.16.218.2:8080/handle/183446/497.
[62] Wang, Yong, Li, Jiang Tao, He, Li Sheng, Yang, Bo, Gao, Zhao Ming, Cao, Hui Luo, Batang, Zenon, AlSuwailem, Abdulaziz, Qian, PeiYuan. Zonation of Microbial Communities by a Hydrothermal Mound in the Atlantis II Deep (the Red Sea). PLOS ONE[J]. 2015, 第 3 作者10(10): http://ir.idsse.ac.cn/handle/183446/1214.
[63] Zhang, Yu, Sun, Jin, Zhang, Huoming, Chandramouli, Kondethimmanahalli H, Xu, Ying, He, LiSheng, Ravasi, Timothy, Qian, PeiYuan. Proteomic profiling during the pre-competent to competent transition of the biofouling polychaete Hydroides elegans. BIOFOULING[J]. 2014, 第 6 作者30(8): 921-928, http://124.16.218.2:8080/handle/183446/754.
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[65] He Lisheng. Characterization of two cp20k homologues in Amphibalanus Amphitrite.. Plos One.. 2013, 第 1 作者
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（ 1 ） ****启动基金, 主持, 部委级, 2013-09--2015-09
（ 2 ） 中国科学院先导专项B, 主持, 部委级, 2014-01--2018-12
（ 3 ） 金星幼虫与成体红巨藤壶（Megabalanus Rosa）胶蛋白的异同, 主持, 国家级, 2015-01--2018-12
（ 4 ） 海斗深渊底栖生物捕捉器的研发, 主持, 研究所（学校）, 2015-01--2016-12
（ 5 ） 系统集成、承载设备研制与海试, 主持, 国家级, 2016-07--2020-06
（ 6 ） 深渊端足类底栖生物肠道共生微生物的比较研究, 主持, 研究所（学校）, 2017-01--2018-12
（ 7 ） 深海贻贝与微生物共生机制的探索, 主持, 部委级, 2013-09--2015-09
（ 8 ） 深渊宏生物的肠道共生微生物与宿主的互利关系, 主持, 国家级, 2018-07--2021-12
（ 9 ） 盲鳗基因组测序、组装及初步分析, 主持, 省级, 2019-12--2022-12
（ 10 ） 源于深海热液虾的抗菌肽的活性研究, 主持, 省级, 2019-10--2021-09
（ 11 ） 三种南海深海钩虾线粒体基因组特征及其进化地位分析, 主持, 省级, 2020-06--2022-05

（1）Vertically transmitted symbiont in the hadal snailfish bridges Mycoplasma and Ureaplasma   2019年度微生物学研讨会   2019-04-08
（2）Genomic characterization of the unique symbiont Ureaplasma liparidae from the gut of hadal snailfish   第十五届深海生物研讨会   2018-09-08
（3）Genomic characterization of Mycoplasma symbiotic bacteria from the stomach of deep-sea isopod Bathynomus sp.   第十六届国际微生物生态学研讨会   2016-08-20
（4）A molecular Study of the gut Content of the Bathynomus giganteus From the South China Sea   第十四届国际深海生物研讨会   2015-08-31
（5）The involvement of the activation of p38 MAPK in barnacle larval settlement.   He L, and Qian PY,    2012-08-01
（6）The involvement of hsc70 and EBV latent membrane protein-1 in the regulation of cell mitosis   He L, and Qi RZ,    2008-11-03
（7）The neuronal p35 activator of Cdk5 regulates microtubule dynamics   He L, Hou Z, and. Qi RZ.    2008-01-01

已指导学生

闫国永  博士研究生  070703-海洋生物学  

李俊元  博士研究生  070703-海洋生物学  

王少露  硕士研究生  070703-海洋生物学  

程项雨  硕士研究生  070703-海洋生物学  

朱方超  博士研究生  070703-海洋生物学  

连春盎  博士研究生  070703-海洋生物学  

现指导学生

廖燕雯  硕士研究生  070703-海洋生物学  

李琪  博士研究生  070703-海洋生物学  

史孟可  博士研究生  070703-海洋生物学