《分生绪论第一次》PPT课件

1,医学分子生物学MedicalMolecularBiology,HonghuaZhengDepartmentofbiochemistry&molecularbiologyTel-mail:safflower6800,2,医学分子生物学人民卫生出版社，药立波主编MolecularBiology，RobertF.Weaver,McGraw-HillCompanies,Inc.，2000（影印版，科学出版社）现代分子生物学（第二版），朱玉贤、李毅编著，高等教育出版社，2002,Referencebooks,3,Thegreatestintellectualrevolutionofthelast40yearsmayhavetakenplaceinbiology.Cananyonebeconsiderededucatedtodaywhodoesnotunderstandalittleaboutmolecularbiology?-F.H.Westheimer,4,TherelationshipbetweenbiochemistryandmolecularbiologyBiochemistrymajorinbiologicalphenomenafromthechemistryangle,especiallyonthestructureandmetabolismchangesofthevariouslivingcreaturemolecules.Molecularbiologyemphasizestheessenceofthelife-Mainlyresearchthestructureandfunctionofhugemolecules(nucleicacidandprotein),deliveringandregulationofgeneinformation.,5,V.ApplicationofMedicalmolecularbiology,I.Whatsmedicalmolecularbiology?,IV.ThefutureofMedicalmolecularbiology,Introduction,III.Thedevelopmentofmedicalmolecularbiology,II.Thecontentsofmedicalmolecularbiology,6,I.Whatsmedicalmolecularbiology?,7,Themolecularbiologyissciencethatresearchesbiologicalphenomena,lifeessenceandlifeactivityanditslawatthemolecularlevel.Itisantheoryandtechniquesystemformedatthemolecularlevel,whichiscalledmolecularbiology.ThebirthofmolecularbiologycanmatchwiththediscoveryofcellandtheestablishingofTheoryofEvolution.Itisoneofthegreatnessachievementsofnaturalsciencein20thcentury.,1.Molecularbiology,8,2.Medicalmolecularbiology,Medicalsciencemolecularbiologyresearchesthelifeactivityanditslawunderthenormalandabnormalconditionofhuman.Itstudiestheprevention,diagnosisandcureofhumandiseasesfromthemoleculehorizontal.,Thebasicmedicalscienceisthefoundationofthewholemedicalscience,whilethemedicalmolecularbiologylinksthebasicmedicalscienceanditseachsub-branchwithclinicalmedicalsciencelikeastring.,9,II.Thecontentsofmedicalmolecularbiology?,10,1.Thestructure&functionofgene&genome,3.Cellscommunication&cellsignaling,4.Geneanalysis,preparation,regulationandapplication,5.Themolecularmechanismofgrowth,development,aging&deathect.,6.Themolecularmechanismofdiseases,2.Thestore,replication,expressing®ulationofgeneticinformation,11,12,III.Thedevelopmentofmedicalmolecularbiology,In1865,GregorMendelpublishedMendelianinheritance(孟德尔遗传定律).,Gardenpea,Inheritanceoccurredthroughblendingofeachtraitoftheparentsintheoffspring.,Inheritanceisparticulate（微粒，微粒的）.Eachparentcontributesparticles,orgeneticunits,totheoffspring.,1822-1884,/RC/AB/BC/Gregor_Mendel.html,GregorMendel,In1910,ThomasHuntMorganprovidedthefirstdefinitiveevidencefortheChromosometheoryofinheritance,1933NobelPrizeinPhysiology/Medicineforhisdiscoveriesconcerningtheroleplayedbythechromosomeinheredity（遗传）,demonstratedthatgenesareonthechromosome“.,fruitfly(Drosophiamelanogaster),1866-1945,/scientists/morgan.htm,ThediscoveryofDNA,1869,FriedrichMiescherdiscoverednucleinandthemajorcomponentofnucleinisDNA.,1844-1895,http:/www.fmi.ch/members/marilyn.vaccaro/ewww/index2.html,TheCompositionofGenes,1944,OswaldAverydemonstratedthatthechromosomeiscomposedofDNA.NotRNAorprotein!,FrederickGriffith肺炎球菌转化试验,1877-1955,/dnaftb/concept_17/con17bio.html,ThediscoveryofDNA,1869,FriedrichMiescherdiscoverednucleinandthemajorcomponentofnucleinisDNA.,1844-1895,http:/www.fmi.ch/members/marilyn.vaccaro/ewww/index2.html,RosalindFrankin,(核与磷酸连接成的扭曲绳子，每一节上都有配对的碱基),1951.KingsLab.LondonUniversityUK,M.H.F.Wilkins,XrayphotographofDNAwithhighquality,JamesWatson(34y)FrancisCrick(46y)MauriceWilkins(46y),1962NobelPrize,Intheearly1960sMarshallNirenbergGobindKhoranaRobertW.Holley,1968NobelPrizeinMedicine,1927-,1922-,1922-,Fortheirinterpretationofthegeneticcodeanditsfunctioninproteinsynthesis.,22,Onegene-oneenzyme,23,桑格Sanger,吉尔伯特Gilbert,伯格Berg,1980Sanger（英）Gilbert&Berg（英）,酶法核苷酸测序的设计者,化学测序法的设计者,DNA重组，在细菌中表达胰岛素DNA重组技术的元老,Sanger还由于测定了牛胰岛素的一级结构而获得1958年诺贝尔化学奖。,24,1989Altman（加）Cech（美）,FounderofRibozyme（核酶）,TheNobelPrizeinChemistry1980,“Fortheircontributionsconcerningthedeterminationofbasesequencesinnucleicacids,WalterGilbert,FrederickSanger,1932-,1918-,TheNobelPrizeinChemistry1989,“RortheirdiscoveryofcatalyticpropertiesofRNARibozyme,SidneyAltman,ThomasR.Cech,YaleUniversityNewHaven,CT,USA,UniversityofColoradoBoulder,CO,USA,1939-,1947-,KaryB.Mullis,1944-,“Forhisinventionofthepolymerasechainreaction(PCR)method,1997，TheNobelPrizeinPhysiologyorMedicine,“ForhisdiscoveryofPrionsanewbiologicalprincipleofinfection,StanleyB.PrusinerUniv.ofCalifornia,SchoolofMedicineUSA1942-,29,30,IV.ThefutureofMedicalmolecularbiology,31,Twomajordirectionsofthecurrentmedicalmolecularbiology:,（1）Constantlyputthetheoryandtechniquesdeepen.,（2）Kepttouchwithandintegratewithothersubjects.,32,Thefourfrontierresearchfieldsatpresent,（1）Structuralmolecularbiology（2）HumanGenomicProject（3）Geneexpressionandregulation（4）Signaltransduction,33,（1）StructuralmolecularbiologyBiologicalfunctiondependsonthestructure.Onlybiomacromoleculeshaveaspecificspacesolidstructure,namelythreedimensionalstructure,cantheyhavephysicalcapabilities.,34,（2）HumanGenomicProjectTheHumanGenomeProject(HGP)isaninternationalscientificresearchprojectwithaprimarygoalofdeterminingthesequenceofchemicalbasepairswhichmakeupDNA,andofidentifyingandmappingtheapproximately20,00025,000genesofthehumangenomefrombothaphysicalandfunctionalstandpoint.,35,Post-genomicsincludes:1）FunctionalGenomics2）proteomics3）comparativegenomics4）cellsplan5）Bioinformaticsandbiochip,36,（3）GeneexpressionandregulatoryresearchGeneexpressionistheprocessbywhichinformationfromageneisusedinthesynthesisofafunctionalgeneproduct.Theseproductsareoftenproteins,butinnon-proteincodinggenessuchasribosomalRNA(rRNA),transferRNA(tRNA)orsmallnuclearRNA(snRNA)genes,theproductisafunctionalRNA.,37,（4）SignaltransductionSignaltransductionistheprocessbywhichanextracellularsignalingmoleculeactivatesamembranereceptor,thatinturnaltersintracellularmoleculescreatingaresponse.Therearetwostagesinthisprocess:asignallingmoleculeactivatesacertainreceptoronthecellmembrane,causingasecondmessengertocontinuethesignalintothecellandelicitaphysiologicalresponse.Ineitherstep,thesignalcanbeamplified,meaningthatonesignalingmoleculecancausemanyresponses.,38,39,V.ApplicationofMedicalmolecularbiology,40,1.Appliedinmedicalbasictheoryresearch,2.Appliedingenediagnosis,3.Appliedingenetherapy,4.Appliedinbioengineeringandbiopharmaceuticals,5.AppliedinPreventiveMedicine,41,1.Thebasisofcellmolecularbiology,Thecellisthestructuralandfunctionalbasicunitoflife.Socellmolecularbiologysresearchisomnibearing,butonthewholeitcomesdowntotwoaspects:1)Howgeneandgeneproductscontrolcellsimportantlifeactivities,suchasgrowth,differentiation,decrepitudeandsoon.2)Howgeneproductsandotherbiomoleculesassemblehighlyorganizedcellstructuresandmakecellscarryonorderedlifeactivities.,42,GenediagnosisisthedetectionofgeneticdisordersbyDNAanalysis.Newgenediagnosismethodsmakeitpossibletofindthechromosomallocationofgenesthatareresponsibleforneurologicalandpsychiatricconditionsandtoidentifystructuralchangesinthesegenesthatareresponsibleforcausingdisease.Thisinformationcanbequiteusefulforidentifyingindividualsthatcarryfaultygenes.,2.Genediagnosis,43,（1）Diagnosegeneticdiseasesbymedicalmolecularbiologytechnology,PCRorSouthernblot.,（2）diagnoseinfectiousdiseasesbymolecularhybridizationandPCR.,（3）detectpointmutationofoncogeneandanti-oncogenebyapplyingPCR/ASOorPCR-SSCP,youcandetectpointmutationofoncogeneandanti-oncogene.,（4）carryonmedicolegalexpertisebysouthernblotandgeneticchip.,44,Withthedevelopmentofgenetherapybasicresearch,nowgenetherapyisnotonlyappliedinsingle-genegeneticdiseases,butalsosomepolygenegeneticdiseases,forexample:polygeneticdiseasesmalignanttumorSomeinfectiousdiseases,suchasAIDScardiovasculardiseases,45,截止到2002年底，全世界批准的基因治疗临床试验方案达