遗传学与分子生物学系

1、遗传学与分子生物学系Molucular BiologyLu Shermin (吕社民)Tel: 82657764Email:遗传学与分子生物学系Lecture I: Introduction Of Molecular Biology1. Definition, Goal and Scope2. Fundamentals3. A brief history4. Methodology of Molecular Biology5. Role in Medical sciences6. prospective遗传学与分子生物学系DefinitionAn elusive term, More than

2、 one definitionStudy 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 遗传学与分子生物学系GoalTo understand the five basic cell behavior patterns

3、(growth, division, specialization, movement, and interaction) in terms of various molecules that are responsible for them遗传学与分子生物学系ScopeStructure and function of Nucleotides and proteinStructure and function of genomeGene proliferation, expression, regulation and biological functionInteraction betwe

4、en biological macromolecules Intra and intermolecular signal transductionTechnology of molecular biology遗传学与分子生物学系Scope of Medical Molecular BiologyMolecular mechanism of cellular growth, differentiation and Senescence in human beingMolecular basis of proliferation and its regulation of human cellsM

5、olecular Biology 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

6、 and health care in terms of theory and technology of molecular biology遗传学与分子生物学系Lecture I: Introduction Of Molecular Biology1. Definition, Goal and Scope2. Fundamentals3. A brief history4. Methodology of Molecular Biology5. Role in Medical sciences6. prospective遗传学与分子生物学系遗传学与分子生物学系“Weak” Interactio

7、ns Chemical bonds (covalent) have energies of 101-2 kcal/mole. STRONGSTRONG Weak interactions Hydrogen bonds 5 kcal/mole Van der Waals interactions 1 kcal/mole “Hydrophobic” interactions Less classifiable, a consequence of other forces遗传学与分子生物学系Hydrophobic interactions Polar materials (water) on bal

8、ance have attractive intermolecular forces. 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 medium遗传学与分子生物学系Nucleotides Base Sugar

9、(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Lecture I: Introduction Of Molecular Biology1. Definition, Goal and Scope2. Fundamentals3. A brief history4. Methodology of Molecular B

10、iology5. Role in Medical sciences6. prospectiveGregor Mendel (1822-1884) MAURICE H. F. WILKINS (1916-) ROSALIND E. FRANKLIN (1920-1958) Linus Carl Pauling (1901-1994) Oswald Theodore Avery (1877-1955)遗传学与分子生物学系A brief history (time line) 1839 Schleiden & Schwann Cell theory 1859 Darwin:1865 Mend

11、el: Genetics1869 Miescher: discovered 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: r

12、ecombinant DNA in vitro1973 Cohen: first used plasmid to clone DNA1977 Gilbert & Sanger: sequence1986 Mullis: PCR1990 Watson et al: Lauched the HGP1997 Wilmut:Dolly1998- Bioinformatics,Proteomes(ome)遗传学与分子生物学系Major Achievements of Molecular Biology after 70sDNA polymerase dependent on RNA (Rever

13、se transcription)Tool enzymes (restrictive endonuclease, DNA ligase, etc)Split geneDNA SequencingMAb RibozymesPCRGene regulationTransgenic organismDNA recombination in intro and in vivo (gene therapy)HGPiRNAProteomicsHapmap (SNPs)BioinformaticsSystems biology遗传学与分子生物学系Lecture I: Introduction Of Mole

14、cular Biology1. Definition, Goal and Scope2. Fundamentals3. A brief history4. Methodology of Molecular Biology5. Role in Medical sciences6. prospective遗传学与分子生物学系Physical and chemical approaches_Ultracentrifuge*20sSize and shape of molecule in centrifugal fieldElectrophoresis* 30s separation of prote

15、in and nucleic acids based on size and/or charge in electric 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 pr

16、otein and nucleic acidAmino acid analysis*50s determination 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 Prize遗传学与分子生物学系Genetic MethodsMutant

17、organisms recoginize a Novel process unravel a comlex metabolic pathway establish a relationship between an identified gene and its previous unknown functionPure genes pin-point substitution or deletion reverse genetics遗传学与分子生物学系Model Biological systemVirusBacteriaBacteriophageYeastWorm (C. elegant)

18、Plant (Arabidopsis)FlyMouseRathuman遗传学与分子生物学系Logic of molecular biologyThe efficiency argumentPhylogenetic historyQuantitative assessmentModel buildingParallelismStrong inferenceOptimism遗传学与分子生物学系Lecture I: Introduction Of Molecular Biology1. Definition, Goal and Scope2. Fundamentals3. A brief histo

19、ry4. Methodology of Molecular Biology5. Role in Medical sciences6. prospective遗传学与分子生物学系 Molecular medicine Molecular immunology Molecular pharmacology Molecular pathology Molecular entomology Molucular Microbiology Molecular taxanomy Molecular biomathmatics Bioinformatics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、

20、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

21、(gene chip)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(gene replacement) 2、基因修正(gene correction) 3、基因增强(gene augmentation) 4、基因抑制(gene constraint)和/或基因 失活(gene inactivation) 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

22、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、DNA footprinting、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

23、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Lecture I: Introduction Of Molecular Biology1. Definition, Goal and Scope2. Fundamentals3. A brief history4. Methodology of Molecular Biology5. Role in Medical sciences