遗传学与分子生物学系.ppt

遗传学与分子生物学系,MolucularBiologyLuShermin(吕社民)Tel:82657764Email:lushemin,遗传学与分子生物学系,LectureI:IntroductionOfMolecularBiology,Definition,GoalandScopeFundamentalsAbriefhistoryMethodologyofMolecularBiologyRoleinMedicalsciencesprospective,遗传学与分子生物学系,DefinitionAnelusiveterm,MorethanonedefinitionStudylife(biology)inmolecularlevelStudygenestructureandfunctionatthemolecularlevel.Grewoutofthedisciplinesofgeneticsandbiochemistry.HybriddisciplineBiochemistryGeneticsMolecularBiologyBiophysics,遗传学与分子生物学系,GoalTounderstandthefivebasiccellbehaviorpatterns(growth,division,specialization,movement,andinteraction)intermsofvariousmoleculesthatareresponsibleforthem,遗传学与分子生物学系,ScopeStructureandfunctionofNucleotidesandproteinStructureandfunctionofgenomeGeneproliferation,expression,regulationandbiologicalfunctionInteractionbetweenbiologicalmacromoleculesIntraandintermolecularsignaltransductionTechnologyofmolecularbiology,遗传学与分子生物学系,ScopeofMedicalMolecularBiologyMolecularmechanismofcellulargrowth,differentiationandSenescenceinhumanbeingMolecularbasisofproliferationanditsregulationofhumancellsMolecularBiologyofthreeregulatorysystems(nervous,endocrineandimmunesystems)inhumanbodyRelationshipbetweenabnormalityofgenestructure,regulationwithetiopathogenesisofhumandiseasesGenediagnosisandgenetherapyintermsoftheoryandtechnologyofmolecularbiologyDrugdiscoveryandhealthcareintermsoftheoryandtechnologyofmolecularbiology,遗传学与分子生物学系,LectureI:IntroductionOfMolecularBiology,Definition,GoalandScopeFundamentalsAbriefhistoryMethodologyofMolecularBiologyRoleinMedicalsciencesprospective,遗传学与分子生物学系,遗传学与分子生物学系,“Weak”Interactions,Chemicalbonds(covalent)haveenergiesof101-2kcal/mole.STRONGWeakinteractionsHydrogenbonds5kcal/moleVanderWaalsinteractions1kcal/mole“Hydrophobic”interactionsLessclassifiable,aconsequenceofotherforces,遗传学与分子生物学系,Hydrophobicinteractions,Polarmaterials(water)onbalancehaveattractiveintermolecularforces.Nonpolarmaterialshavenoparticulartendencytoassociate.Result:Nonpolarmaterialswithinanaqueouscompartmentassociatebecausetheyareexcludedbythemutuallyattractiveforcesbetweenthemoleculesofthemedium,遗传学与分子生物学系,Nucleotides,BaseSugar(Base+Sugar=Nucleoside)Phosphate(Nucleoside+phosphate=Nucleotide),遗传学与分子生物学系,遗传学与分子生物学系,遗传学与分子生物学系,遗传学与分子生物学系,遗传学与分子生物学系,遗传学与分子生物学系,遗传学与分子生物学系,遗传学与分子生物学系,遗传学与分子生物学系,LectureI:IntroductionOfMolecularBiology,Definition,GoalandScopeFundamentalsAbriefhistoryMethodologyofMolecularBiologyRoleinMedicalsciencesprospective,GregorMendel(1822-1884),MAURICEH.F.WILKINS(1916-),ROSALINDE.FRANKLIN(1920-1958),LinusCarlPauling(1901-1994),OswaldTheodoreAvery(1877-1955),遗传学与分子生物学系,Abriefhistory(timeline)1839Schleiden&SchwannCelltheory1859Darwin:1865Mendel:Genetics1869Miescher:discoveredDNA1902SuttenChromosome1910,1916Morgan:geneareonchromosomes1944Avery:identifiedDNAasthematerialgenesaremadeof1953WatsonCrick：DNAstructure1958Meselson&Stahl:semiconservativereplicationofDNA1961Jacobetal:discoveredmRNA1972Berg:recombinantDNAinvitro1973Cohen:firstusedplasmidtocloneDNA1977Gilbert&Sanger:sequence1986Mullis:PCR1990Watsonetal:LauchedtheHGP1997Wilmut:Dolly1998-Bioinformatics,Proteomes(ome),遗传学与分子生物学系,MajorAchievementsofMolecularBiologyafter70sDNApolymerasedependentonRNA(Reversetranscription)Toolenzymes(restrictiveendonuclease,DNAligase,etc)SplitgeneDNASequencingMAbRibozymesPCRGeneregulationTransgenicorganismDNArecombinationinintroandinvivo(genetherapy)HGPiRNAProteomicsHapmap(SNPs)BioinformaticsSystemsbiology,遗传学与分子生物学系,LectureI:IntroductionOfMolecularBiology,Definition,GoalandScopeFundamentalsAbriefhistoryMethodologyofMolecularBiologyRoleinMedicalsciencesprospective,遗传学与分子生物学系,Physicalandchemicalapproaches_Ultracentrifuge*20sSizeandshapeofmoleculeincentrifugalfieldElectrophoresis*30sseparationofproteinandnucleicacidsbasedonsizeand/orchargeinelectricfieldElectronMicroscope30sdirectlyvisualizationofcellarultra-structure,includingDNARadioisotopetracers*40strackingflowofmoleculethroughametabolicpathwayX-raydiffraction*50sprovidesprecisemeasurementof3-DstructureofproteinandnucleicacidAminoacidanalysis*50sdeterminationoforderofaminoacidinproteinNucleicacidhybridization60squantitativeassessmentofsimilarityofRNAsorDNAsRecombinantDNA*70sgeneticengineeringofnovelgenes-*DenotesassociatedwithNobelPrize,遗传学与分子生物学系,GeneticMethodsMutantorganismsrecoginizeaNovelprocessunravelacomlexmetabolicpathwayestablisharelationshipbetweenanidentifiedgeneanditspreviousunknownfunctionPuregenespin-pointsubstitutionordeletionreversegenetics,遗传学与分子生物学系,ModelBiologicalsystemVirusBacteriaBacteriophageYeastWorm(C.elegant)Plant(Arabidopsis)FlyMouseRathuman,遗传学与分子生物学系,LogicofmolecularbiologyTheefficiencyargumentPhylogenetichistoryQuantitativeassessmentModelbuildingParallelismStronginferenceOptimism,遗传学与分子生物学系,LectureI:IntroductionOfMolecularBiology,Definition,GoalandScopeFundamentalsAbriefhistoryMethodologyofMolecularBiologyRoleinMedicalsciencesprospective,遗传学与分子生物学系,MolecularmedicineMolecularimmunologyMolecularpharmacologyMolecularpathologyMolecularentomologyMolucularMicrobiologyMoleculartaxanomyMolecularbiomathmaticsBioinformatics,遗传学与分子生物学系,发育、分化与衰老细胞增殖调控神径、内分泌和免疫调控致病基因和易感基因的鉴定和克隆,遗传学与分子生物学系,脑和神经生物学神经系统发育、信号传递：最富挑战性、最复杂的问题之一。脑约有3万个基因处于表达状态分子水平揭示脑的思维、记忆和学习等功能治疗精神病,遗传学与分子生物学系,基因诊断,特异性强、灵敏度高、简便快速。遗传病（优生优育）传染病(包括HIV)现已发展到对一些常见病(如糖尿病、动脉粥样硬化及精神分裂症等)的诊断，还应用于结核病、肝炎、传染病及恶性肿瘤的诊断及法医学鉴定。主要限制是造成疾病的基因突变多样性，妨碍针对所有疾病进行分子诊断试验的设计。,遗传学与分子生物学系,基因诊断技术,PCR技术核酸探针杂交技术基因芯片(genechip)技术限制性片段长度多态性(RFLP)单核苷酸多态性(SNP)发展趋势：“自动化”、“程序化”、“非标记技术”和“多病种”等特色。,遗传学与分子生物学系,基因治疗,1、基因替代(genereplacement)2、基因修正(genecorrection)3、基因增强(geneaugmentation)4、基因抑制(geneconstraint)和/或基因失活(geneinactivation)5、反义疗法,遗传学与分子生物学系,基因治疗希望与局限,（1）基因治疗癌症未获进展（2）仅限于治疗少数疾病，费用昂贵（3）导入人体的目的基因表达水平（4）获得长期表达效果难,遗传学与分子生物学系,在中药学中的应用,蛋白质或酶技术核酸技术：药用植物鉴别、RFLP、RAPD、DNAfootprinting、biochip药用植物育种药用植物次生代谢产物,遗传学与分子生物学系,生物制药,按生物化学性质分为：氨基酸类、有机酸、醇酮类、维生素、酶及辅酶类、脂类、多肽和蛋白质类、核酸类及其衍生物、多糖等。按生物工程学科分为：基因工程制药(上百种多肽药物)、细胞工程制药、微生物工程制药和酶工程制药四大类。转基因的动植物,遗传学与分子生物学系,生物制药发展趋势,1、动物细胞高效表达和细胞大量培养。2、蛋白质工程和蛋白质杂交研究。3、药物剂型研究。4、药物配伍研究。5、基础医学的生物技术研究。6、研究开发第二代生物技术药物，即核酸、糖、脂类三类药物。,遗传学与分子生物学系,疫苗研制,1、亚基疫苗2、多肽疫苗3、活体重组疫苗4、多价疫苗5、DNA疫苗:流感DNA、狂犬病DNA疫苗、乙肝DNA疫苗、结核病DNA疫苗、疟疾DNA疫苗,遗传学与分子生物学系,环境监测与净化基因探针：饮用水，6000儿童/天死“超级菌”、“超级质粒”：辛烷、已烷和癸烷、二甲苯和甲苯、樟脑、萘，石油中的烃类化合物重金属、致癌物、农药和杀虫剂,遗传学与分子生物学系,LectureI:IntroductionOfMolecularBiology,Definition,GoalandScopeFundamentalsAbriefhistoryMethodologyofMolecularBiologyRoleinMedicalsciencesprospective,遗传学与分子生物学系,人类重大疾病蛋白质组学建立国际水平的技术平台选择与人类重要生命活动相关的系统、器官、细