欧竑宇 的个人介绍页
欧竑宇
欧竑宇
教授
...
bioinfo-mml.sjtu.edu.cn
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个人简历

欧竑宇,男,1976年生,博士,上海交通大学生命科学技术学院/微生物代谢国家重点实验室,微生物学教授。1997年本科毕业于南京农业大学食品工程专业,2001年于天津科技大学获发酵工程硕士学位,2004年于天津大学获生物信息学博士学位;后赴英国莱斯特大学从事病原菌基因组学博士后研究。2006年6月起在上海交通大学工作,历任微生物学副教授、教授。近八年来以重要耐药性条件致病菌和主要抗生素产生菌链霉菌为研究体系,建立了以生物信息学和分子遗传学交叉支撑的细菌基因组岛研究平台。在细菌基因组岛研究工具和数据库开发、遗传学分析等研究取得了一定的系统性进展。至2014年2月已发表SCI收录论文37篇。其中,在Nucleic Acids Research (7篇)和Journal of Molecular Diagnostics等专业刊物中发表通讯作者或第一作者(含并列)论文17篇,累计SCI影响因子达88,SCI他引累计超170次,单篇最高SCI他引33次。相关工作得到了包括Science, Nature Microbiology Reviews, Annual Review of Genetics, Annual Review of Microbiology, Trends in Microbiology, Critical Reviews in Microbiology, Microbiology and Molecular Biology Reviews, Biotechnology Advances等杂志的他人引用。我们四次受国内外知名学者邀请撰写专著章节或综述,分别由Springer、John Wiley & Sons、科学出版社和“微生物学通报”出版。到上海交通大学工作后,主持了4项国家自然科学基金面上项目 (含青年基金) 及1项863计划课题;多次担任Nucleic Acids Research, Bioinformatics, BMC Genomics, BMC Microbiology等十余个国际刊物审稿人;多次在首届亚洲生物技术大会 (ACB 2011)、第十五届国际生物技术大会 (IBS 2012)、第十五届国际放线菌生物学大会 (ISBA’15)和中国微生物学学术年会等专业学术会议上担任分会场主持人或作口头报告;入选教育部新世纪优秀人才资助计划、上海市青年科技启明星计划、上海市明治乳业生命科学奖、上海交通大学晨星青年学者奖励计划SMC优秀青年教师 (A类)、全国优秀博士学位论文提名论文。

研究方向

生物信息学导向的细菌基因组岛遗传学研究
细菌常通过质粒、原噬菌体、整合子和基因组岛等可移动元件获得致病和耐药等新性状,维持或增强了其在特定选择压力下的竞争优势和遗传稳定性。我们结合生物信息学方法和分子遗传学实验技术,系统地开展了细菌基因组岛介导致病和耐药基因水平转移的分子机制研究。围绕耐药性条件致病菌基因组岛的识别、转移和调控分析,我们研发和维护了一系列特色生物信息学工具和数据库,长期免费向国内外同行提供基因组岛预测工具、基于并行计算的细菌基因组序列快速比对等服务,以及整合性接合元件、IV型分泌系统和II型毒素-抗毒素等分子生物学数据库。我们比较分析了基因组岛在不同来源肺炎克雷伯菌中分布;预测了沙门氏菌的甲型副伤寒血清型特有基因,多重PCR检测确定了高敏感度和特异度;发现了DNA硫修饰及其限制系统以基因组岛的形式广泛分布于细菌和古细菌中。近年来的主要研究进展简述如下:

(1)细菌基因组岛分析的特色工具集和开放数据库

(I) 岛的计算识别:随着同个种属中多个甚至几十个不同来源菌株完成基因测序,需要快速识别这些亲缘菌中各自特有的基因组岛,迅速实现基因型到独特表型的功能解析。我们提出了搜索临床菌株基因组岛的新策略MobilomeFINDER,核心技术包括“tRNAcc工具识别岛插入热点,PCR技术搜索岛,酵母捕捉质粒克隆新岛” [Ou, et al. (2007) Nucleic Acids Research, 2007]。MobilomeFINDER论文已被包括Nature Microbiology Reviews, Microbiology and Molecular Biology Reviews, Biotechnology Advances和Bacterial Molecular Networks: Methods in Molecular Biology (Spring)等刊物或专著上的论文所引用。该策略已成功应用于指导肺炎克雷伯菌、鲍曼不动杆菌、肠道沙门氏菌和铜绿假单胞菌等重要条件致病菌中,发现基因组岛的分子遗传学实验研究。此外,我们研发的在线工具mGenomeSubtractor利用并行计算技术实现了多个基因组序列的快速对比 [Shao, et al. (2010) Nucleic Acids Research]。mGenomeSubtractor可在~5分钟内高速识别出至多四十个细菌基因组的菌株特异基因。2010年在发表以来,mGenomeSubtractor向国内和国际上的微生物学同行提供了长年的免费在线计算服务。

(II) 岛的水平转移:整合性接合元件 (ICEs) 是一种可自主移动的典型基因组岛,是介导细菌致病和耐药性传播的一种有效途径;但目前所发现的ICEs仅是冰山一角。我们通过文献挖掘和计算预测构建了细菌整合性接合元件数据库ICEberg,系统地收录了上百个细菌中400多个ICEs [Bi, et al. (2012) Nucleic Acids Research]。细菌整合性接合元件数据库ICEberg最近为PLoS Genetics、Genome Biology、Journal of Bacteriology、Journal of Antimicrobial Chemotherapy、Critical Reviews in Microbiology、Management of Microbial Resource in the Environment (Spring)等刊物或专著上的论文提供了数据支持。“The conservation and diversity of bacterial integrative and conjugative elements”论文获2012年中国微生物学会学术年会优秀学术论文交流奖。而SecReT4数据库则收录了细菌八百多个介导ICE接合转移的IV型分泌系统,对1万多个T4SS组分和近两千个效应蛋白进行了功能描述 [Bi, et al. (2013) Nucleic Acids Research]。

(III) 岛遗传稳定性的调控:受体菌常借助与细胞程序性死亡相关的毒素-抗毒素系统来调控可移动元件的遗传稳定性。II型毒素-抗毒素系统的毒素和抗毒素基因组成一个操纵子结构,抗毒素为不稳定的蛋白质,能够与相应的毒素蛋白结合中和毒性。毒素-抗毒素系统广泛存在于质粒和细菌基因组岛上。我们开发的细菌毒素-抗毒素系统数据库TADB比较分析了1万多个的II型毒素-抗毒素系统,按毒素蛋白序列及三级结构相似性归纳为14个家族 [Shao, et al. (2011) Nucleic Acids Research]。TADB数据库为Science, Nature Microbiology Reviews, Annual Review of Genetics, Annual Review of Microbiology, Trends in Microbiology, Critical Reviews in Microbiology, Molecular Cell上发表的论文或综述提供了数据支持。

(2)重要条件致病菌基因组岛的功能解析和应用
条件致病菌肺炎克雷伯菌是院内感染最重要的革兰氏阴性耐药菌之一。我们长期广泛收集了不同来源的肺炎克雷伯菌,进行了比较基因组分析。菌株库包括各种敏感临床株、多重耐药株、化学品生产株、及来源于水稻、玉米和红树林根际的环境株。通过MobilomeFINDER策略考察了这些不同生境肺炎克雷伯菌的基因组多样性,发现了十多个新基因组岛 [Chen, et al. (2010) Current Microbiology; Zhang, et al. (2011) Journal of Microbiological Methods]。近期,我们报道了耐碳青霉烯类的肺炎克雷伯菌HS11286基因组全序列,该菌株分离于上海地区病人痰液、属于ST11型的中国流行株 [Liu, et al. (2012) Journal of Bacteriology]。其中一个大质粒有接合转移系统,并携带blaKPC-2基因,使该菌对亚胺培南等碳青霉烯类抗生素产生抗性。更值得关注的是,一个ICE不仅包含耶尔森高致病岛 (HPI,编码重要致病因子耶尔森杆菌素),而且有完整功能的IV型分泌系统。我们推测该ICE有可能介导耶尔森杆菌素在肠杆菌科中快速散播。基于这些工作,我们受邀撰写了“高通量发现菌株特异性DNA的方法”(Handbook of Molecular Microbial Ecology I, F. J. de Bruijn主编, John Wiley & Sons Inc. 出版社,2011) 和“基于比较基因组学的细菌基因组岛识别与功能分析”(中国微生物基因组研究,喻子牛主编,科学出版社,2012)等专著章节。“重要条件致病菌可移动基因组的比较分析”论文获2010年中国微生物学会学术年会优秀学术论文交流奖。我们正在从事新岛对应表型的鉴定和关键代谢调控通路的解析。
我们以血清型特异的靶基因为切入点,尝试将基因组岛比较分析应用于临床病原菌的分子检测。肠道沙门氏菌是一类常见的食源病原菌。我们与英国莱斯特大学和马来西亚马来亚大学合作,在利用MobilomeFINDER对多株已测序沙门氏菌基因组比较分析后,识别了在东南亚地区广泛流行的甲型副伤寒沙门菌的特异靶基因。对52个甲型副伤寒沙门氏菌、75个其他血清型沙门氏菌及15个非沙门氏菌的常见食源病原菌,采用多重PCR进行检测,敏感度和特异度均为100%。[Ou, et al. (2007) Journal of Molecular Diagnostics]。

(3)其他细菌基因组岛比较分析的相关研究
我们利用海量组学数据挖掘的研究经验,积极与多个实验型研究组展开了优势互补的合作。对于重要抗生素产菌链霉菌,我们侧重选择了可移动遗传元件编码的菌株独特性状来展开“干-湿”合作研究。令人鼓舞的是,合作研究发现了DNA硫修饰系统通过水平转移以基因组岛的形式,广泛存在于分类地位和生态差异很大的细菌和古细菌中,包括变铅青链霉菌、大肠杆菌、肠道沙门氏菌、铜绿假单胞菌和肺炎克雷伯菌等 [Ou, et al. (2009) PloS One, 2009; He, et al. (2007) Molecular Microbiology]。对天蓝色链霉菌基因组岛深入分析,首次发现了DNA硫修饰依赖的限制系统,其中一个岛编码了能切割磷硫酰化DNA的IV型核酸内切酶 [Liu, et al. (2010) PloS Genetics]。这些合作结晶有助于阐明DNA硫修饰的生物学意义。此外,我们合作完成了目前发现的唯一产天然氟化物的卡特利链霉菌DSM 46488全基因组测序,鉴定了合成氟化物的必须基因散布于该基因组的两个复制子中 [Zhao, et al. (2012) Bioorganic Chemistry]。发现了该菌两个线性复制子的特殊结构: 一条“相对小于其他链霉菌”的染色体 (6.3 Mb),和一个目前报道的最大的巨型质粒 (1.8 Mb)。此外,我们还采用隐马尔科夫模型来表征硫肽生物合成关键酶的序列保守性,合作开发了硫肽数据库ThioBase和硫肽合成基因簇的识别工具ThioFinder [Li, et al. (2012) PloS One]。以上工作应邀在“微生物学通报 (2013年放线菌专刊) ”上发表了“链霉菌基因组岛和次生代谢物合成相关的生物信息学工具及数据库”的综述。

发表论文

书籍章节:
(i) H.Y. Ou*, Y. Wei, D. Bi (2013) Book chapter: “Type II Loci: Phylogeny”, Prokaryotic Toxin-Antitoxins, Editor Kenn Gerdes, Springer.
(ii) H.Y. Ou* and K. Rajakumar* (2011) Book chapter: “ArrayOme- & tRNAcc-facilitated mobilome discovery: comparative genomics approaches for identifying rich veins of bacterial novel DNA sequences”, Handbook of Molecular Microbial Ecology I: Metagenomics and Complementary Approaches, Editor F. J. de Bruijn, John Wiley & Sons, Inc.
(iii) 欧竑宇 (2012)“基于比较基因组学的细菌基因组岛识别与功能分析”, 中国微生物基因组研究, 喻子牛等主编, 科学出版社.

研究论文
(37) D. Bi, L. Liu, C. Tai, Z. Deng, K. Rajakumar* and H.Y. Ou* (2013) SecReT4: a web-based bacterial type IV secretion system resource. Nucleic Acids Research, 41, D660-D665.
(36) F. Su, H.Y. Ou, F. Tao, H. Tang and P. Xu* (2013) PSP: rapid identification of orthologous coding genes under positive selection across multiple closely related prokaryotic genomes. BMC Genomics, 14:924
(35) D. Bi, Z. Xu, E. Harrison, C. Tai, Y. Wei, X. He, S. Jia, Z. Deng, K. Rajakumar* and H.Y. Ou* (2012) ICEberg: a web-based resource for integrative and conjugative elements found in Bacteria. Nucleic Acids Research, 40, D621-D626.
(34) P. Liu, P. Li, X. Jiang, D. Bi, Y. Xie, C. Tai, Z. Deng, K. Rajakumar and H.Y. Ou* (2012) Complete Genome Sequence of Klebsiella pneumoniae subsp. pneumoniae HS11286, a Multidrug-Resistant Strain Isolated from Human Sputum. Journal of Bacteriology, 194, 1841-1842.
(33) C. Zhao, P. Li, Z. Deng, H.Y. Ou *, R.P. McGlinchey, D. O'Hagan * (2012) Insights into fluorometabolite biosynthesis in Streptomyces cattleya DSM46488 through knockout mutants. Bioorganic Chemistry, 44, 1-7.
(32) J. Li, X. Qu, X. He, L. Duan, G. Wu, D. Bi, Z. Deng, W. Liu*, H.Y. Ou* (2012) ThioFinder: a web-based tool for the identification of thiopeptide gene clusters in DNA sequences. PloS ONE, 7, e45878.
(31) M. Kochar, M. Crosatti, E.M. Harrison, B. Rieck, J. Chan, C. Constantinidou, M. Pallen, H.Y. Ou and K. Rajakumar (2012) Deletion of TnAbaR23 results in both expected and unexpected antibiogram changes in a multi-drug resistant Acinetobacter baumannii strain. Antimicrob Agents Chemother, 56, 1845-1853.
(30) J.J. van Aartsen, S.G. Stahlhut, E.M. Harrison, M. Crosatti, H.Y. Ou, K.A. Krogfelt, C. Struve and K. Rajakumar (2012) Characterization of a novel chaperone/usher fimbrial operon present on KpGI-5, a methionine tRNA gene-associated genomic island in Klebsiella pneumoniae. BMC Microbiology, 12, 59.
(29) B. Rieck, D. Tourigny, M. Crosatti, R. Schmid, M. Kochar, E. Harrison, H.Y. Ou, J. Turton and K. Rajakumar (2012) Acinetobacter insertion sequence ISAba11 belongs to a novel family that encodes transposases with a signature HHEK motif. Applied and Environmental Microbiology, 78, 471-480.
(28) Y. Shao, E.M. Harrison, D. Bi, C. Tai, X. He, H.Y. Ou*, K. Rajakumar and Z. Deng (2011) TADB: a web-based resource for Type 2 toxin-antitoxin loci in bacteria and archaea. Nucleic Acids Research, 39, D606-D611.
(27) J. Zhang, J. Jurriaan van Aartsen, X. Jiang, Y. Shao, C. Tai, X. He, Z. Tan, Z. Deng, S. Jia*, K. Rajakumar and H.Y. Ou* (2011) Expansion of the known Klebsiella pneumoniae species gene pool by characterization of novel alien DNA islands integrated into tmRNA gene sites. Journal of Microbiological Methods, 84, 283-289.
(26) F. Su, B. Yu, J. Sun, H.Y. Ou, B. Zhao, L. Wang, J. Qin, H. Tang, F. Tao, M. Jarek, M. Scharfe, C. Ma, Y. Ma, P. Xu (2011) Genome sequence of thermophilic strain Bacillus coagulans 2-6, an efficient producer of high optical purity L-lactic acid. Journal of Bacteriology, 193, 4563-4.
(25) D.Q. Wu, J. Ye, H.Y. Ou, X. Wei, X. Huang , Y.W. He and Y. Xu (2011) Genomic analysis and temperature-dependent transcriptome profiles of the rhizosphere originating strain Pseudomonas aeruginosa M18. BMC Genomics, 2011, 12:438.
(24) G. Liu, H.Y. Ou, T. Wang, L. Li, H. Tan, X. Zhou, K. Rajakumar, Z. Deng* and X. He* (2010) Cleavage of Phosphothioated DNA and Methylated DNA by the Type IV Restriction Endonuclease ScoMcrA. PLoS Genetics, 6, e1001253.
(23) Y. Shao, X. He, C. Tai, H.Y. Ou*, K. Rajakumar and Z. Deng (2010) mGenomeSubtractor: a web-based tool for parallel in silico subtractive hybridization analysis of multiple bacterial genomes. Nucleic Acids Research, 38, W194-W200.
(22) N. Chen¶, H.Y. Ou¶, J.J. van Aartsen, X. Jiang, M. Li, Z. Yang, Q.Wei, X. Chen, X. He, Z.Deng, K. Rajakumar,Y. Lu (2010) The pheV phenylalanine tRNA gene in Klebsiella pneumoniae clinical isolates is an integration hotspot for possible niche-adaptation genomic islands. Current Microbiology, 60, 210-6. ( ¶ These authors contributed equally to this work.)
(21) J. Sridhar, S.R. Narmada, R. Sabarinathan, H.Y. Ou, Z. Deng, K. Sekar, Z.A. Rafi, K. Rajakumar (2010) sRNAscanner: a computational tool for intergenic small RNA detection in bacterial genomes. PLoS ONE, 5, e11970.
(20) E.M. Harrison, M.E.K. Carter, S. Luck, H.Y. Ou, X. He, Z. Deng, C. Oallaghan, A. Kadioglu and K. Rajakumar (2010) The pathogenicity islands PAPI-1 and 2 PAPI-2 contribute individually and synergistically to virulence of Pseudomonas aeruginosa strain PA14. Infection and Immunity, 78, 1437-1446.
(19) H.Y. Ou, X. He, Y. Shao, C. Tai, K. Rajakumar and Z. Deng* (2009) dndDB: a database focused on phosphorothioation of the DNA backbone. PLoS ONE, 4, e5132.
(18) F. Wang, X. Xiao, H.Y. Ou, Y. Gai, F. Wang (2009) The role and regulation of fatty acid biosynthesis in Shewanella piezotolerans WP3 response to different temperatures and pressures. Journal Bacteriology, 191, 2574-84.
(17) F. Shaikh, R.P. Spence, K. Levi, H.Y. Ou, Z. Deng, K.J. Towner and K. Rajakumar (2009) ATPase genes of diverse multi-drug resistant Acinetobacter baumannii isolates frequently harbour integrated DNA. Journal of Antimicrobial Chemotherapy, 63, 260-4.
(16) J. Malkin, P.T. Kimmitt, H.Y. Ou, P.S. Bhasker, M. Khare, Z. Deng, I. Stephenson, A.W. Sosnowski, N. Perera and K. Rajakumar (2008) Identification of Streptococcus gallolyticus subsp. macedonicus as the etiological agent in a case of culture-negative multivalve infective endocarditis by 16S rDNA PCR analysis of resected valvular tissue. Journal of Heart Valve Disease, 17, 589-92.
(15) H.Y. Ou ¶, C.T.S. Ju ¶, K.L. Thong, N. Ahmad, Z. Deng, M.R. Barer and K. Rajakumar* (2007). Translational Genomics to Develop a Salmonella enterica Serovar Paratyphi A Multiplex PCR Assay. Journal of Molecular Diagnostics, 2007, 9, 624-630. (¶ These authors contributed equally to this work.) (Cover Figure and Comment in: J Mol Diagn. 2007, 9, 572-573.)
(14) H.Y. Ou, X. He, E.M. Harrison, B.R. Kulasekara, A.B. Thani, A. Kadioglu, S. Lory, J.C. Hinton, M.R. Barer, Z. Deng* and K. Rajakumar* (2007). MobilomeFINDER: web-based tools for in silico and experimental discovery of bacterial genomic islands. Nucleic Acids Research, 35, W97-W104.
(13) X. He, H.Y. Ou, Q. Yu, X. Zhou, J. Wu, J. Liang, W. Zhang, K. Rajakumar and Z. Deng* (2007). Analysis of a genomic island housing genes for DNA S-modification system in Streptomyces lividans 66 and its counterparts in other distantly related bacteria. Molecular Microbiology, 65, 1034-48.
(12) H.Y. Ou, L.L. Chen, J. Lonnen, R.R. Chaudhuri, A.B. Thani, R. Smith, N.J. Garton, J.C. Hinton, M. Pallen, M. Barer and K. Rajakumar (2006). A novel strategy for identification of genomic islands by comparative analysis of the contents and contexts of tRNA sites in closely related bacteria. Nucleic Acids Research, 34, e3.
(11) H.Y. Ou , R. Smith, S. Lucchini, J.C. Hinton, R.R. Chaudhuri, M. Pallen, M. Barer and K. Rajakumar (2005). ArrayOme: a program for estimating the sizes of the microarray-visualised genomes. Nucleic Acids Research, 33, e3.
(10) W.X. Zheng, L.L. Chen, H.Y. Ou, F. Gao and C.T. Zhang (2005). Coronavirus phylogeny based on a geometric approach. Molecular Phylogenetics and Evolution, 36, 224-232.
(9) H.Y. Ou, F.B. Guo and C.T. Zhang (2004). GS-Finder: a program to find bacterial gene start sites with a self-training method. Int. J. Biochem. Cell Biol. 36, 535-544.
(8) R. Zhang, H.Y. Ou and C.T. Zhang (2004). DEG, a Database of Essential Genes. Nucleic Acids Research, 32, D271-D272.
(7) S.R. Jia, H.Y. Ou, G.B. Chen, D.B. Choi, K.A. Cho, M. Okabe and W.S. Cha (2004). Cellulose Production from Gluconobacter oxydans TQ-B2. Biotechnology and Bioprocess Engineering 9, 166-170.
(6) H.Y. Ou, F.B. Guo and C.T. Zhang (2003). Analysis of nucleotide distribution in the genome of Streptomyces coelicolor A3(2) using the Z curve method. FEBS Letters 540, 188-194.
(5) F.B. Guo, H.Y. Ou and C.T. Zhang (2003). ZCURVE: a new system for recognizing protein-coding genes in bacterial and archaeal genomes. Nucleic Acids Research, 31, 1780-1789.
(4) C.T. Zhang, R. Zhang and H.Y. Ou (2003). The Z curve database: a graphic representation of genome sequences. Bioinformatics 19, 593-599.
(3) Y.H. Wang, H.Y. Ou and F.B. Guo (2003). Recognition of translation initiation sites of eukaryotic genes based on EM algorithm. Journal of Computational Biology, 10, 699-708.
(2) L.L. Chen¶, H.Y. Ou¶, R. Zhang and C.T. Zhang (2003). ZCURVE_CoV: a new system to recognize protein coding genes in coronavirus genomes, and its applications in analyzing SARS-CoV genomes. Biochem. Biophys. Res. Commun. 307, 382-388. (¶ These authors contributed equally to this work.)
(1) F. Gao, H.Y. Ou, L.L. Chen, W.X. Zheng and C.T. Zhang (2003). Prediction of proteinase cleavage sites in polyproteins of coronaviruses and its applications in analyzing SARS-CoV genomes. FEBS Letters, 553, 451-456.

研究成果

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