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1、1医学分子生物学医学分子生物学MedicalMolecular BiologyHonghua ZhengDepartment of biochemistry&molecular biologyTel:13275020171E-mail:2医学分子生物学医学分子生物学人民卫生出版社,药立波主编人民卫生出版社,药立波主编Molecular Biology,Robert F.Weaver,McGraw-Hill Companies,Inc.,2000(影印版,(影印版,科学出版社)科学出版社)现代分子生物学现代分子生物学(第二版),朱玉贤、李毅编(第二版),朱玉贤、李毅编著,高等教育出版社,著,高等
2、教育出版社,2002Reference books3The greatest intellectual revolution of the last 40 years may have taken place in biology.Can anyone be considered educated today who does not understand a little about molecular biology?-F.H.Westheimer4 The relationship between biochemistry and molecular biologyBiochemistr
3、y major in biological phenomena from the chemistry angle,especially on the structure and metabolism changes of the various living creature molecules.Molecular biology emphasizes the essence of the life-Mainly research the structure and function of huge molecules(nucleic acid and protein),delivering
4、and regulation of gene information.5V.Application of Medical molecular biologyMedical molecular biologyI.Whats medical molecular biology?IV.The future of Medical molecular biologyIntroductionIII.The development of medical molecular biologyII.The contents of medical molecular biology6I.Whats medical
5、molecular biology?7 The molecular biology is science that researches biological phenomena,life essence and life activity and its law at the molecular level.It is an theory and technique system formed atthe molecular level,which is called molecular biology.The birth of molecular biology can match wit
6、h the discovery of cell and the establishing of Theory of Evolution.It is one of the greatness achievements of natural science in 20th century.1.Molecular biology82.Medical molecular biology Medical science molecular biology researches the life activity and its law under the normal and abnormal cond
7、ition of human.It studies the prevention,diagnosis and cure of human diseases from the molecule horizontal.The basic medical science is the foundation of the whole medical science,while the medical molecular biology links the basic medical science and its each sub-branch with clinical medical scienc
8、e like a string.9II.The contents of medical molecular biology?10 1.The structure&function of gene&genome1.The structure&function of gene&genome3.Cells communication 3.Cells communication&cell signaling cell signaling 4.Gene analysis,preparation,regulation and 4.Gene analysis,preparation,regulation a
9、nd applicationapplication5.The molecular mechanism of growth,development,5.The molecular mechanism of growth,development,aging&death aging&death ectect.6.The molecular mechanism of6.The molecular mechanism ofdiseasesdiseases2.The store,replication,expressing®ulation of genetic information2.The st
10、ore,replication,expressing®ulation of genetic information1112III.The development of medical molecular biologyIn 1865,Gregor Mendel published Mendelian inheritance(孟德尔遗传定律孟德尔遗传定律).GardenpeaInheritance occurred through blending of each trait of the parents in the offspring.Inheritance is particulat
11、e(微粒,微粒的)(微粒,微粒的).Each parent contributes particles,or genetic units,to the offspring.1822-1884http:/www.accessexcellence.org/RC/AB/BC/Gregor_Mendel.htmlGregor MendelIn 1910,Thomas Hunt Morganprovidedthefirstdefinitiveevidenceforthe Chromosome theory of inheritance 1933 Nobel Prizein Physiology/Medi
12、cine forhisdiscoveriesconcerningtheroleplayedbythechromosomeinheredity(遗传),demonstrated that genes are on the chromosome“.fruitfly(Drosophia melanogaster)1866-1945http:/www.geneticstv.org/scientists/morgan.htmThe discovery of DNA1869,Friedrich Miescherdiscoverednucleinandthemajorcomponentofnucleinis
13、DNA.1844-1895http:/www.fmi.ch/members/marilyn.vaccaro/ewww/index2.htmlThe Composition of Genes1944,Oswald AverydemonstratedthatthechromosomeiscomposedofDNA.NotRNAorprotein!FrederickGriffith肺炎球菌转化试验肺炎球菌转化试验1877-1955http:/www.dnaftb.org/dnaftb/concept_17/con17bio.htmlThe discovery of DNA1869,Friedrich
14、 MiescherdiscoverednucleinandthemajorcomponentofnucleinisDNA.1844-1895http:/www.fmi.ch/members/marilyn.vaccaro/ewww/index2.htmlRosalindFrankin(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.LondonUniversityUKM.H.F.WilkinsXray photograph of DNA with high qualityJames Watson(34y)Francis Crick(46y)Maurice Wilk
15、ins(46y)1962 Nobel PrizeIntheearly1960sMarshall NirenbergGobind Khorana Robert W.Holley1968 Nobel Prize in Medicine1927-1922-1922-For their interpretation of the genetic code and its function in protein synthesis.1975.Howard Temin(41y)David Baltimore(37y)Reverse transcription(引发癌症的内因)(引发癌症的内因)22One
16、gene-one enzymeBeadle Tatum23桑格桑格 Sanger 吉尔伯特吉尔伯特 Gilbert 伯格伯格 Berg 1980 Sanger(英)(英)Gilbert&Berg(英)(英)酶法核苷酸测酶法核苷酸测序的设计者序的设计者化学测序法的设计者化学测序法的设计者DNADNA重组,在细菌中表重组,在细菌中表达胰岛素达胰岛素DNADNA重组技术的元老重组技术的元老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。年诺贝尔化学奖。24 1989 Altman(加)(加)Cech(美)(美)Founder of Ribo
17、zyme(核酶核酶)Sidney AltmanThomas R.CechThe Nobel Prize in Chemistry 1980“For their contributions concerning the determination of base sequences in nucleic acidsWalter GilbertFrederick Sanger1932-1918-1983.Barbara McClintock(86y)DNA transposable elementThe Nobel Prize in Chemistry 1989“Ror their discove
18、ry of catalytic properties of RNA RibozymeSidney AltmanThomas R.CechYaleUniversityNewHaven,CT,USAUniversityofColoradoBoulder,CO,USA1939-1947-The Nobel Prize in Chemistry 1993Kary B.Mullis1944-“For his invention of the polymerase chain reaction(PCR)method1997,The Nobel Prize in Physiology or Medicine
19、 “For his discovery of Prions a new biological principle of infectionStanley B.Prusiner Univ.of California,School of Medicine USA 1942-2930IV.The future of Medical molecular biology31Two major directions of the current medical molecular biology:(1)Constantly put the theory and techniques deepen.(2)K
20、ept touch with and integrate with other subjects.32The four frontier research fields at present(1)Structural molecular biology(2)Human Genomic Project(3)Gene expression and regulation(4)Signal transduction33(1)Structural molecular biologyBiologicalfunctiondependsonthestructure.Onlybiomacromoleculesh
21、aveaspecificspacesolidstructure,namelythreedimensionalstructure,cantheyhavephysicalcapabilities.34 (2)Human Genomic ProjectTheHuman Genome Project(HGP)isaninternationalscientificresearchprojectwithaprimarygoalofdeterminingthesequenceofchemicalbasepairswhichmakeupDNA,andofidentifyingandmappingtheappr
22、oximately20,00025,000genesofthehumangenomefrombothaphysicalandfunctionalstandpoint.35 Post-genomics includes:1)Functional Genomics 2)proteomics 3)comparative genomics 4)cells plan 5)Bioinformatics and biochip36 (3)Gene expression and regulatory research Gene expressionistheprocessbywhichinformationf
23、romageneisusedinthesynthesisofafunctionalgeneproduct.Theseproductsareoftenproteins,butinnon-proteincodinggenessuchasribosomalRNA(rRNA),transferRNA(tRNA)orsmallnuclearRNA(snRNA)genes,theproductisafunctionalRNA.37 (4)Signal transduction Signal transductionistheprocessbywhichanextracellularsignalingmol
24、eculeactivatesamembranereceptor,thatinturnaltersintracellularmoleculescreatingaresponse.Therearetwostagesinthisprocess:asignallingmoleculeactivatesacertainreceptoronthecellmembrane,causingasecondmessengertocontinuethesignalintothecellandelicitaphysiologicalresponse.Ineitherstep,thesignalcanbeamplifi
25、ed,meaningthatonesignalingmoleculecancausemanyresponses.3839V.Application of Medical molecular biology401.Applied in medical basic theory research 2.Applied in gene diagnosis3.Applied in gene therapy4.Applied in bioengineering and biopharmaceuticals5.Applied in Preventive Medicine411.The basis of ce
26、ll molecular biologyThecellis the structural and functional basic unit oflife.So cell molecular biologys research is omnibearing,but on the whole it comes down to two aspects:1)How gene and gene products control cells important life activities,such as growth,differentiation,decrepitude and so on.2)H
27、ow gene products and other biomolecules assemble highly organized cell structures and make cells carry on ordered life activities.42GenediagnosisisthedetectionofgeneticdisordersbyDNAanalysis.Newgenediagnosismethodsmakeitpossibletofindthechromosomallocationofgenesthatareresponsibleforneurologicalandp
28、sychiatricconditionsandtoidentifystructuralchangesinthesegenesthatareresponsibleforcausingdisease.Thisinformationcanbequiteusefulforidentifyingindividualsthatcarryfaultygenes.2.Gene diagnosis43(1)Diagnose genetic diseases by medical molecular biology technology,PCRorSouthern blot.(2)diagnose infecti
29、ous diseases by molecular hybridization and PCR.(3)detect point mutation of oncogene and anti-oncogene by applying PCR/ASO or PCR-SSCP,you can detect point mutation of oncogene and anti-oncogene.(4)carry on medicolegal expertise by southern blot and genetic chip.44With the development of gene therap
30、y basic research,now gene therapy is not only applied in single-gene genetic diseases,but also some polygene genetic diseases,for example:polygenetic diseasesmalignant tumorSome infectious diseases,such as AIDScardiovascular diseases45截止到2002年底,全世界批准的基因治疗临床试验方案达到了636个,病人数量3 496个。在所批准的基因治疗临床试验方案中,美国占
31、了大多数,共有505个,占了总数的79.4%;其次是欧洲103个,占总数的16.2%;亚洲共有9个,仅占总数的1.4%。V.Application of Medical molecular biology47Transgenic animalsTransgenic animals猪、牛、羊、鱼等猪、牛、羊、鱼等Transgenic plantsTransgenic plants抗虫棉、耐贮藏番茄等抗虫棉、耐贮藏番茄等抗棉铃虫棉花抗棉铃虫棉花1.The improvement of biodiversity48把人的基因成功转入猪的受精卵细胞把人的基因成功转入猪的受精卵细胞中,繁殖出了基因工程猪
32、,尝试利用猪的器中,繁殖出了基因工程猪,尝试利用猪的器官进行异种移植。官进行异种移植。2.Organ transplants49 生物工程广泛用于生物制药领域。目前采用基因生物工程广泛用于生物制药领域。目前采用基因工程制备的多肽药物已达工程制备的多肽药物已达100多种,如干扰素、白介多种,如干扰素、白介素、生长激素、红细胞生成素、免疫球蛋白等。素、生长激素、红细胞生成素、免疫球蛋白等。3.Biopharmaceuticals从人血中提取从人血中提取1mg干扰素,需要人血干扰素,需要人血8000ml,其成本高得惊人。,其成本高得惊人。要获取要获取1磅(磅(453g)纯干扰素,其成本)纯干扰素,其
33、成本高达高达200亿美元亿美元。现在要获取现在要获取1磅(磅(453g)纯干扰素,其)纯干扰素,其成本不到成本不到1亿美元。亿美元。50Examples of genetically engineered drugs in the world5152Vaccine researchOther applicationsEnvironmental monitoring and purifying53Whatarethemaincontentsofmedicalmolecularbiology?Whataremedicalmolecularbiologytechniquesmainlyused?Questions54Assessment MethodsAssignments 20Attendance 10Final exam 70Attention55医学分子生物学教学进度医学分子生物学教学进度Broad range of study Keeping pace with the timesPositive thinkingHope
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