毕利军研究员
LijunBi,Professor

专家类别:研究员
简历&研究组工作摘要：2004-至今,在中科院生物物理研究所主要从事生物大分子相互作用，分子识别和生物传感器,蛋白质组学，纳米分子机器等研究工作;2003-2004在日本KINKIUNIVERSITY从事博士后研究，主要从事动物胚胎细胞的蛋白质组学;2000-2003于中科院武汉病毒所攻读博士学位,主要从事DNA错配修复系统的基础和应用研究.目前主要从事DNA损伤修复与癌症发生以及结核分支杆菌的耐药机理研究.作为项目/课题负责人先后承担了国家自然科学基金项目、中国科学院创新基地重要方向项目和国家重大基础研究计划项目等。主要研究方向：DNA损伤修复。近期主要工作和进展DNA损伤是基因突变的诱因，导致基因组的不稳定性。细胞依赖各种修复系统对其损伤进行修复。已有证据显示人类DNA修复失活导致基因组DNA的高突变率，并引起多种癌症的发生，但具体的修复机制、各种修复途径、细胞周期调控及凋亡如何协同作用以保持基因组的稳定性和防止癌症的发生还远不清楚。结核病是由结核杆菌引起的全球性传染疾病。由于基因突变导致的耐药性使人类对其防治更加困难。结核杆菌缺乏明显的错配修复基因、具有高突变率和易形成耐药性，目前还不了解这三个特征是否存在内在联系。课题组围绕上述问题开展研究，主要工作概括为四个方面：1）DNA修复机制：完成了修复蛋白MutS寻找错配位点和UvrD的解螺旋功能可视化研究；研究修复蛋白MutL与DNA聚合酶III的相互作用揭示了DNA错配修复与复制系统的协同作用机制。2）结核杆菌DNA修复与耐药性：完成了吡嗪酰胺酶的鉴定及其突变情况调查工作；开展GyraseB结构与功能研究；建立DNA修复蛋白库并开展DNA修复和耐药性的研究。3）非编码RNA与DNA修复：垂钓ncRNA的靶蛋白并研究其功能；研究ncRNA对DNA修复功能的调控；开展结核杆菌ncRNA标注。4）分析生物技术：开展蛋白激酶检测肽芯片和基因突变检测等方法研究。

Biography&Introduction1997-2000Master,ShenyangAgriculturalUniversity,PRChina2000-2003PhD,WuhanInstituteofVirology,CAS2003-2004Postdoctoralresearcher,KinkiUniversity,Japan2004-atpresent,Prof.InstituteofBiophysics,CASDNArepairsystemtakesanimportantroleinkeepingstabilityofgenomeanditsdefectinthemammalianpathwayisassociatedwithastrongpredispositiontotumordevelopment.Sofar,detailmechanismislessunderstood.Tuberculosisisoneofthemostdeadlyandcommoninfectiousdiseases,whoseglobalspreadisfurthercomplicatedbytheubiquitousappearanceofdrug-resistantstrains.OurworkhasbeenfocusedonthemechanismofDNAdamagerepairandtherelationshipbetweenDNArepairanddrug-resistance.Furtherdetailsaregivenbelow:1)DNArepairsystem:(a)thesestudiesonthemechanismofMutSsearchingforamismatchsiteandvisualizationandkineticanalysisofDNAbindingandunwindingbyHelicaseII(UvrD)havebeendone.(b)WefindthestrongevidencetosupportthenotionthatDNAreplicationandMMRarehighlyassociatedwitheachother.2)DNArepairanddrug-resistanceofMTB:(a)CharacterizationofPncAandresearchontherelationshipofitsmutationanddrug-resistancehavebeenfinished.(b)StudiesonstructureandfunctionofGyraseBhavebeendeveloped.(c)WeareconstructingalibrarycomposedofDNArepairproteinsofMTBanddoingtherelativeworksonDNArepairanddrug-resistance.3)Non-codingRNAandDNArepair:(a)wearebaitingthetargetproteinofncRNAintheC.elegansandfurthertodiscovertheirfunctions.(b)researchonregulationofncRNAonDNArepairfunctioninhumanisdoing.(c)wearefocusingonfindingncRNAsanddiscoveringtheirfunctionsinmycobacteriumtuberculosis.4)analyticalmethods:theyincludepeptidechipsfordetectionofproteinkinase,detectionofgenemutationandsoon.
SelectedPublications1.ThedimerstateofGyrBofMycobacteriumtuberculosisisanactiveform:implicationsfortheinitialcomplexassemblyandprocessivestrandpassage.JinjunWu,etal.Xian-EnZhang*andLijunBi*.NucleicAcidResearch,2011.2.ASir2-likeproteinparticipatesinMycobacteriumtuberculosisNHEJ.ZhongdaoLietal.,Li-JunBi*andXian-EnZhang*.PlosOne,2011.3.QuantitativeProteomicAnalysisofTumorReversioninMultipleMyelomaCells.FengGeetal.,Li-JunBi*,JProteomeRes.2011,10:845-855.4.CrystalstructureofDNAgyraseB'domainofMycobacteriumtuberculosisshedslightsonthemechanismforT-segmentnavigation.FuGetal.,BiL*andWangDC*.NucleicAcidsRes.2009,37,5908-5916.5.ConstructionandCharacterizationofDifferentMutSFusionProteinsasRecognitionElementsofDNAChipforDetectionofDNAMutationsinMycobacteriumtuberculosis.LJBIetal.,Xian-EnZHANG*.BiosensorsandBioelectronics,2005,21:135-144.6.AMutSbasedproteinchipfordetectionofDNAmutationsinMycobacteriumtuberculosis.LJBIetal.,XEZhang*.AnalChem,2003,75,4113-4119.7.AsimplifiedmethodforreconstitutingactiveE.coliDNApolymeraseIII.Shi-qiangLin,Li-junBi*andXian-enZhang*.Proteinandcell,2011.2(4):303–307.8.Wen-JunGui,Shi-QiangLin,Yuan-YuanChen,Xian-EnZhang,Li-JunBi*,TaoJiang*.CrystalstructureofDNApolymeraseIIIbetaslidingclampfromMycobacteriumtuberculosis,BiochemicalBiophysicalResearchCommunication,2011,405:272-277.9.MutS-mediatedenrichmentofmutatedDNAproducedbydirectedevolutioninvitro.TianyingZhong?YafengZhou?LijunBi?Xian-EnZhang.WorldJournalofMicrobiologyandBiotechnology.2011
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