AssociateInvestigator,NIBS,Beijing,ChinaPhone:010-80726688-8505
Fax:010-80726689
E-mail:dulilin@nibs.ac.cn
教育经历Education1992南开大学生物系,学士
B.Sc.,DepartmentofBiology,NankaiUniversity,China
1995中国科学院上海生物化学研究所,硕士
M.Sc.,ShanghaiInstituteofBiochemistry,ChineseAcademyofSciences,China
2001耶鲁大学分子生物物理学与生物化学系,博士
Ph.D.,DepartmentofMolecularBiophysics&Biochemistry(MB&B),YaleUniversity,USA
工作经历ProfessionalExperience2001-2007美国斯克利普斯研究院,PaulRussell博士实验室,博士后
PostdoctoralResearchAssociateinDr.PaulRussell'slabatTheScrippsResearchInstitute(TSRI),USA
2007-2013北京生命科学研究所研究员
AssistantInvestigator,NationalInstituteofBiologicalSciences,Beijing,China
2013北京生命科学研究所高级研究员
AssociateInvestigator,NationalInstituteofBiologicalSciences,Beijing,China
研究概述:本实验室利用裂殖酵母开展研究。作为一种单细胞真核模式生物,裂殖酵母具有培养简便、实验周期短、遗传学手段强大、多数基因与人类基因同源等优势,特别适于深入解析基本生命过程背后的机理。另外,裂殖酵母紧凑的基因组和丰富的组学工具使它成为系统生物学研究的一个高效平台。因此,我们的研究方向既包括对特定通路分子机制的探索,同时也利用高通量技术开展遗传相互作用的大规模筛选,以期得到对系统层次规律的新认识。1.DNA双链断裂的修复机制DNA双链断裂是对基因组稳定性破坏力最大的一类DNA损伤。我们利用荧光蛋白标记的全蛋白质组文库对参与双链断裂应答的蛋白进行了系统的筛选鉴定。从筛选得到的线索出发开展研究,我们发现了若干新的参与DNA修复的蛋白,其中一个蛋白对两种结构特异性核酸酶有重要的调控作用。我们目前正在开展对其分子机理的研究。2.自噬的研究自噬是运送胞质中的蛋白和细胞器到溶酶体的一个转运途径。在外界营养缺乏时自噬会被上调,通过自我消化的方式提供细胞生理活动所需的原材料。自噬的异常与多种人类疾病相关。我们用正向遗传筛选的方法找到了多个以前未知的自噬基因,并通过反向遗传学分析发现了特异性运送某些蛋白到溶酶体的一个新的转运途径。进一步的研究有望加深我们对自噬和其它类似转运途径的分子机制的理解。3.必需基因省却抑制子的系统筛选必需基因是敲除之后致死的基因。省却抑制子是能够让必需基因变得可省却的遗传改变。利用新一代测序技术,我们建立了高效筛选几种不同类型的省却抑制子的手段。目前,通过对一百多个必需基因所做的筛选,我们已经发现了几十个可省却的必需基因,并正在鉴定它们的省却抑制子。系统地分析这一类极端的遗传相互作用将促进我们对基因功能和基因组进化的认识。ResearchDescription:WeusethefissionyeastSchizosaccharomycespombeasamodelsystem.Workingwithfissionyeasthasmanyadvantages,includingtheeaseofgeneticsandcellbiology,availabilityofpowerfulfunctionalgenomicstools,andextensivehomologybetweenitsgenesandhumangenes.Wearecarryingoutresearchonthefollowingtopics:1.StudyingthemechanismsofDNAdoublestrandbreakrepair.2.Dissectingthemolecularmachineriesofautophagyandrelatedtraffickingpathways.3.Systematicscreeningofgeneticinteractions.Publications:1.SunL-L,LiM,SuoF,LiuX-M,ShenE-Z,YangB,DongM-Q,HeW-Z,andDuL-L.Globalanalysisoffissionyeastmatinggenesrevealsnewautophagyfactors.PLoSGenet.9:e1003715(2013).
2.YuY,RenJ-Y,ZhangJ-M,SuoF,FangX-F,WuF,andDuL-L.Aproteome-widevisualscreenidentifiesfissionyeastproteinslocalizingtoDNAdouble-strandbreaks.DNARepair12:433-443(2013).
3.ZhouZ-X,ZhangM-J,PengX,TakayamaY,XuX-Y,HuangL-Z,andDuL-L.MappinggenomichotspotsofDNAdamagebyasingle-strand-DNA-compatibleandstrand-specificChIP-seqmethod.GenomeRes.23:705-715(2013).
4.QuM,YangB,TaoL,YatesJR3rd,RussellP,DongM-Q,andDuL-L.Phosphorylation-dependentinteractionsbetweenCrb2andChk1areessentialforDNAdamagecheckpoint.PLoSGenet.8:e1002817(2012).
5.LiP,LiJ,LiM,DouK,ZhangM-J,SuoF,andDuL-L.MultipleendjoiningmechanismsrepairachromosomalDNAbreakinfissionyeast.DNARepair11:120–130(2012).
6.LiJ,ZhangJ-M,LiX,SuoF,ZhangM-J,HouW,HanJ,andDuL-L.ApiggyBactransposon-basedmutagenesissystemforthefissionyeastSchizosaccharomycespombe.NucleicAcidsRes.39:e40(2011).
7.SofuevaS,DuL-L,LimboO,WilliamsJS,andRussellP.BRCTdomaininteractionswithphospho-histoneH2AtargetCrb2tochromatinatdouble-strandbreaksandmaintaintheDNAdamagecheckpoint.Mol.Cell.Biol.30:4732–4743(2010).
8.LiuN-N,HanTX,DuL-L,andZhouJ-Q.Agenome-widescreenforSchizosaccharomycespombedeletionmutantsthataffecttelomerelength.CellRes.20:963–965(2010).
9.HanTX,XuX-Y,ZhangM-J,PengX,andDuL-L.Globalfitnessprofilingoffissionyeastdeletionstrainsbybarcodesequencing.GenomeBiol.11:R60(2010).
10.MartínV,DuL-L,RozenzhakS,andRussellP.ProtectionoftelomeresbyaconservedStn1-Ten1complex.Proc.Natl.Acad.Sci.U.S.A.104:14038–14043(2007).
11.DuL-L,NakamuraTM,andRussellP.Histonemodification-dependentand-independentpathwaysforrecruitmentofcheckpointproteinCrb2todouble-strandbreaks.GenesDev.20:1583–1596(2006).
12.CoulonS,NoguchiE,NoguchiC,DuL-L,NakamuraTM,andRussellP.Rad22Rad52-dependentrepairofribosomalDNArepeatscleavedbySlx1-Slx4endonuclease.Mol.Biol.Cell.17:2081–2090(2006).
13.NakamuraTM,MoserBA,DuL-L,andRussellP.CooperativecontrolofCrb2byATMfamilyandCdc2kinasesisessentialfortheDNAdamagecheckpointinfissionyeast.Mol.Cell.Biol.25:10721–10730(2005).
14.DuL-L,MoserBA,andRussellP.Homo-oligomerizationistheessentialfunctionofthetandemBRCTdomainsinthecheckpointproteinCrb2.J.Biol.Chem.279:38409–38414(2004).
15.NakamuraTM,DuL-L,RedonC,andRussellP.HistoneH2AphosphorylationcontrolsCrb2recruitmentatDNAbreaks,maintainscheckpointarrest,andinfluencesDNArepairinfissionyeast.Mol.Cell.Biol.24:6215–6230(2004).
16.NoguchiE,NoguchiC,DuL-L,andRussellP.Swi1preventsreplicationforkcollapseandcontrolscheckpointkinaseCds1.Mol.Cell.Biol.23:7861–7874(2003).
17.DuL-L,NakamuraTM,MoserBA,andRussellP.RetentionbutnotrecruitmentofCrb2atdouble-strandbreaksrequiresRad1andRad3complexes.Mol.Cell.Biol.23:6150–6158(2003).
18.DuL-L,andNovickP.Pag1p,anovelproteinassociatedwithproteinkinaseCbk1p,isrequiredforcellmorphogenesisandproliferationinSaccharomycescerevisiae.Mol.Biol.Cell.13:503–514(2002).
19.ZhangX,BiE,NovickP,DuL,KozminskiKG,LipschutzJH,andGuoW.Cdc42interactswiththeexocystandregulatespolarizedsecretion.J.Biol.Chem.276:46745–46750(2001).
20.DuLL,andNovickP.YeastrabGTPase-activatingproteinGyp1plocalizestotheGolgiapparatusandisanegativeregulatorofYpt1p.Mol.Biol.Cell.12:1215–1226(2001).
21.DuLL,andNovickP.PurificationandpropertiesofaGTPase-activatingproteinforyeastRabGTPases.Meth.Enzymol.329:91–99(2001).
22.ZhaoF,XuS,DuL,andXuG.AMPmakesnativesnakemusclefructose-1,6-bisphosphatasetoanalkalineenzyme.Sci.China,C,LifeSci.43:1–7(2000).
23.DuLL,CollinsRN,andNovickPJ.IdentificationofaSec4pGTPase-activatingprotein(GAP)asanovelmemberofaRabGAPfamily.J.Biol.Chem.273:3253–3256(1998).