遺傳學(xué)與分子生物學(xué)系

1、遺傳學(xué)與分子生物學(xué)系Molucular BiologyLu Shermin (呂社民)Tel: 82657764Email:1遺傳學(xué)與分子生物學(xué)系Lecture I: Introduction Of Molecular BiologyDefinition, Goal and ScopeFundamentalsA brief historyMethodology of Molecular BiologyRole in Medical sciencesprospective2遺傳學(xué)與分子生物學(xué)系DefinitionAn elusive term, More than one definitionS

2、tudy life (biology) in molecular levelStudy gene structure and function at the molecular level.Grew out of the disciplines of genetics and biochemistry.Hybrid discipline BiochemistryGeneticsMolecular BiologyBiophysics 3遺傳學(xué)與分子生物學(xué)系GoalTo understand the five basic cell behavior patterns (growth, divisi

3、on, specialization, movement, and interaction) in terms of various molecules that are responsible for them4遺傳學(xué)與分子生物學(xué)系ScopeStructure and function of Nucleotides and proteinStructure and function of genomeGene proliferation, expression, regulation and biological functionInteraction between biological

4、macromolecules Intra and intermolecular signal transductionTechnology of molecular biology5遺傳學(xué)與分子生物學(xué)系Scope of Medical Molecular BiologyMolecular mechanism of cellular growth, differentiation and Senescence in human beingMolecular basis of proliferation and its regulation of human cellsMolecular Biol

5、ogy of three regulatory systems (nervous, endocrine and immune systems) in human bodyRelationship between abnormality of gene structure, regulation with etiopathogenesis of human diseasesGene diagnosis and gene therapy in terms of theory and technology of molecular biologyDrug discovery and health c

6、are in terms of theory and technology of molecular biology6遺傳學(xué)與分子生物學(xué)系Lecture I: Introduction Of Molecular BiologyDefinition, Goal and ScopeFundamentalsA brief historyMethodology of Molecular BiologyRole in Medical sciencesprospective7遺傳學(xué)與分子生物學(xué)系8遺傳學(xué)與分子生物學(xué)系“Weak” InteractionsChemical bonds (covalent)

7、have energies of 101-2 kcal/mole. STRONGWeak interactionsHydrogen bonds 5 kcal/moleVan der Waals interactions 1 kcal/mole“Hydrophobic” interactionsLess classifiable, a consequence of other forces9遺傳學(xué)與分子生物學(xué)系Hydrophobic interactionsPolar materials (water) on balance have attractive intermolecular forc

8、es.Nonpolar materials have no particular tendency to associate.Result: Nonpolar materials within an aqueous compartment associate because they are excluded by the mutually attractive forces between the molecules of the medium10遺傳學(xué)與分子生物學(xué)系NucleotidesBaseSugar (Base + Sugar = Nucleoside)Phosphate (Nucl

9、eoside + phosphate = Nucleotide)11遺傳學(xué)與分子生物學(xué)系12遺傳學(xué)與分子生物學(xué)系13遺傳學(xué)與分子生物學(xué)系14遺傳學(xué)與分子生物學(xué)系15遺傳學(xué)與分子生物學(xué)系16遺傳學(xué)與分子生物學(xué)系17遺傳學(xué)與分子生物學(xué)系18遺傳學(xué)與分子生物學(xué)系19遺傳學(xué)與分子生物學(xué)系Lecture I: Introduction Of Molecular BiologyDefinition, Goal and ScopeFundamentalsA brief historyMethodology of Molecular BiologyRole in Medical sciencesprospec

10、tive20Gregor Mendel (1822-1884) 2122MAURICE H. F. WILKINS (1916-) ROSALIND E. FRANKLIN (1920-1958) 23Linus Carl Pauling (1901-1994) Oswald Theodore Avery (1877-1955)24遺傳學(xué)與分子生物學(xué)系A(chǔ) brief history (time line) 1839 Schleiden & Schwann Cell theory 1859 Darwin:1865 Mendel: Genetics1869 Miescher: discovered

11、 DNA1902 SuttenChromosome1910,1916 Morgan: gene are on chromosomes1944 Avery:identified DNA as the material genes are made of 1953 Watson Crick：DNA structure1958 Meselson & Stahl:semiconservative replication of DNA1961 Jacob et al: discovered mRNA1972 Berg: recombinant DNA in vitro1973 Cohen: first

12、used plasmid to clone DNA1977 Gilbert & Sanger: sequence1986 Mullis: PCR1990 Watson et al: Lauched the HGP1997 Wilmut:Dolly1998- Bioinformatics,Proteomes(ome)25遺傳學(xué)與分子生物學(xué)系Major Achievements of Molecular Biology after 70sDNA polymerase dependent on RNA (Reverse transcription)Tool enzymes (restrictive

13、endonuclease, DNA ligase, etc)Split geneDNA SequencingMAb RibozymesPCRGene regulationTransgenic organismDNA recombination in intro and in vivo (gene therapy)HGPiRNAProteomicsHapmap (SNPs)BioinformaticsSystems biology26遺傳學(xué)與分子生物學(xué)系Lecture I: Introduction Of Molecular BiologyDefinition, Goal and ScopeFu

14、ndamentalsA brief historyMethodology of Molecular BiologyRole in Medical sciencesprospective27遺傳學(xué)與分子生物學(xué)系Physical and chemical approaches_Ultracentrifuge*20sSize and shape of molecule in centrifugal fieldElectrophoresis* 30s separation of protein and nucleic acids based on size and/or charge in elect

15、ric fieldElectron Microscope30sdirectly visualization of cellar ultra-structure, including DNARadioisotope tracers*40stracking flow of molecule through a metabolic pathwayX-ray diffraction*50sprovides precise measurement of 3-D structure of protein and nucleic acidAmino acid analysis*50s determinati

16、on of order of amino acid in proteinNucleic acid hybridization 60squantitative assessment of similarity of RNAs or DNAsRecombinant DNA *70sgenetic engineering of novel genes-* Denotes associated with Nobel Prize28遺傳學(xué)與分子生物學(xué)系Genetic MethodsMutant organismsrecoginize a Novel processunravel a comlex met

17、abolic pathwayestablish a relationship between an identified gene and its previous unknown functionPure genespin-point substitution or deletionreverse genetics29遺傳學(xué)與分子生物學(xué)系Model Biological systemVirusBacteriaBacteriophageYeastWorm (C. elegant)Plant (Arabidopsis)FlyMouseRathuman30遺傳學(xué)與分子生物學(xué)系Logic of mo

18、lecular biologyThe efficiency argumentPhylogenetic historyQuantitative assessmentModel buildingParallelismStrong inferenceOptimism31遺傳學(xué)與分子生物學(xué)系Lecture I: Introduction Of Molecular BiologyDefinition, Goal and ScopeFundamentalsA brief historyMethodology of Molecular BiologyRole in Medical sciencesprosp

19、ective32遺傳學(xué)與分子生物學(xué)系 Molecular medicine Molecular immunology Molecular pharmacology Molecular pathology Molecular entomology Molucular Microbiology Molecular taxanomy Molecular biomathmatics Bioinformatics33遺傳學(xué)與分子生物學(xué)系發(fā)育、分化與衰老細(xì)胞增殖調(diào)控神徑、內(nèi)分泌和免疫調(diào)控致病基因和易感基因的鑒定和克隆34遺傳學(xué)與分子生物學(xué)系 腦和神經(jīng)生物學(xué)神經(jīng)系統(tǒng)發(fā)育、信號傳遞：最富挑戰(zhàn)性、最復(fù) 雜的問題

20、之一。腦約有3萬個基因處于表達(dá)狀態(tài) 分子水平揭示腦的思維、記憶和學(xué)習(xí)等功能治療精神病 35遺傳學(xué)與分子生物學(xué)系基因診斷特異性強、靈敏度高、簡便快速。遺傳病（優(yōu)生優(yōu)育）傳染病(包括HIV)現(xiàn)已發(fā)展到對一些常見病 (如糖尿病、動脈粥樣硬化及精神分裂癥等)的診斷，還應(yīng)用于結(jié)核病、肝炎、傳染病及惡性腫瘤的診斷及法醫(yī)學(xué)鑒定。主要限制是造成疾病的基因突變多樣性，妨礙針對所有疾病進(jìn)行分子診斷試驗的設(shè)計。 36遺傳學(xué)與分子生物學(xué)系基因診斷技術(shù)PCR技術(shù) 核酸探針雜交技術(shù) 基因芯片(gene chip)技術(shù) 限制性片段長度多態(tài)性(RFLP) 單核苷酸多態(tài)性(SNP) 發(fā)展趨勢 ：“自動化”、“程序化”、“非標(biāo)記

21、技術(shù)”和“多病種”等特色 。37遺傳學(xué)與分子生物學(xué)系基因治療1、基因替代(gene replacement) 2、基因修正(gene correction) 3、基因增強(gene augmentation) 4、基因抑制(gene constraint)和/或基因 失活(gene inactivation) 5、反義療法 38遺傳學(xué)與分子生物學(xué)系基因治療希望與局限（1）基因治療癌癥未獲進(jìn)展（2）僅限于治療少數(shù)疾病，費用昂貴（3）導(dǎo)入人體的目的基因表達(dá)水平（4）獲得長期表達(dá)效果難39遺傳學(xué)與分子生物學(xué)系在中藥學(xué)中的應(yīng)用蛋白質(zhì)或酶技術(shù)核酸技術(shù)：藥用植物鑒別、RFLP、RAPD、DNA footp

22、rinting、biochip藥用植物育種藥用植物次生代謝產(chǎn)物40遺傳學(xué)與分子生物學(xué)系生物制藥按生物化學(xué)性質(zhì)分為：氨基酸類、有機酸、醇酮類、維生素、酶及輔酶類、脂類、多肽和蛋白質(zhì)類、核酸類及其衍生物、多糖等。按生物工程學(xué)科分為：基因工程制藥(上百種多肽藥物)、細(xì)胞工程制藥、微生物工程制藥和酶工程制藥四大類。轉(zhuǎn)基因的動植物 41遺傳學(xué)與分子生物學(xué)系生物制藥發(fā)展趨勢1、動物細(xì)胞高效表達(dá)和細(xì)胞大量培養(yǎng)。 2、蛋白質(zhì)工程和蛋白質(zhì)雜交研究。 3、藥物劑型研究。 4、藥物配伍研究。 5、基礎(chǔ)醫(yī)學(xué)的生物技術(shù)研究。 6、研究開發(fā)第二代生物技術(shù)藥物，即核 酸、糖、脂類三類藥物。 42遺傳學(xué)與分子生物學(xué)系疫苗研制

23、 1、亞基疫苗 2、多肽疫苗 3、活體重組疫苗 4、多價疫苗 5、DNA疫苗:流感DNA 、狂犬病DNA疫苗 、乙肝DNA疫苗 、結(jié)核病DNA疫苗 、瘧疾DNA疫苗 43遺傳學(xué)與分子生物學(xué)系環(huán)境監(jiān)測與凈化基因探針：飲用水，6000兒童/天死“超級菌”、 “超級質(zhì)?！保盒镣?、已烷和癸烷、二甲苯和甲苯、樟腦、萘，石油中的烴類化合物重金屬、致癌物、農(nóng)藥和殺蟲劑 44遺傳學(xué)與分子生物學(xué)系Lecture I: Introduction Of Molecular BiologyDefinition, Goal and ScopeFundamentalsA brief historyMethodology of Molecular BiologyRole in Medical sciencesprospecti