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遗传学与分子生物学系 PowerPoint Presentation
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遗传学与分子生物学系

遗传学与分子生物学系

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遗传学与分子生物学系

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  1. Molucular Biology Lu Shermin (吕社民) Tel: 82657764 Email:lushemin@mail.xjtu.edu.cn 遗传学与分子生物学系

  2. Lecture I: Introduction Of Molecular Biology • Definition, Goal and Scope • Fundamentals • A brief history • Methodology of Molecular Biology • Role in Medical sciences • prospective 遗传学与分子生物学系

  3. Definition • An elusive term, More than one definition • Study life (biology) in molecular level • Study gene structure and function at the molecular level. Grew out of the disciplinesof genetics andbiochemistry. • Hybrid discipline • Biochemistry Genetics Molecular Biology Biophysics 遗传学与分子生物学系

  4. Goal To understand the five basic cell behavior patterns (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

  5. Scope • Structure and function of Nucleotides and protein • Structure and function of genome • Gene proliferation, expression, regulation and biological function • Interaction between biological macromolecules • Intra and intermolecular signal transduction • Technology of molecular biology 遗传学与分子生物学系

  6. Scope of Medical Molecular Biology • Molecular mechanism of cellular growth, differentiation and Senescence in human being • Molecular basis of proliferation and its regulation of human cells • Molecular Biology of three regulatory systems (nervous, endocrine and immune systems) in human body • Relationship between abnormality of gene structure, regulation with etiopathogenesis of human diseases • Gene diagnosis and gene therapy in terms of theory and technology of molecular biology • Drug discovery and health care in terms of theory and technology of molecular biology 遗传学与分子生物学系

  7. Lecture I: Introduction Of Molecular Biology • Definition, Goal and Scope • Fundamentals • A brief history • Methodology of Molecular Biology • Role in Medical sciences • prospective 遗传学与分子生物学系

  8. 遗传学与分子生物学系

  9. “Weak” Interactions • Chemical bonds (covalent) have energies of ~101->2 kcal/mole. STRONG • 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

  10. Hydrophobic interactions • Polar materials (water) on balance 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

  11. Nucleotides • Base • Sugar (Base + Sugar = Nucleoside) • Phosphate (Nucleoside + phosphate = Nucleotide) 遗传学与分子生物学系

  12. 遗传学与分子生物学系

  13. 遗传学与分子生物学系

  14. 遗传学与分子生物学系

  15. 遗传学与分子生物学系

  16. 遗传学与分子生物学系

  17. 遗传学与分子生物学系

  18. 遗传学与分子生物学系

  19. 遗传学与分子生物学系

  20. Lecture I: Introduction Of Molecular Biology • Definition, Goal and Scope • Fundamentals • A brief history • Methodology of Molecular Biology • Role in Medical sciences • prospective 遗传学与分子生物学系

  21. Gregor Mendel (1822-1884)

  22. MAURICE H. F. WILKINS (1916-) ROSALIND E. FRANKLIN (1920-1958)

  23. Linus Carl Pauling (1901-1994) Oswald Theodore Avery (1877-1955)

  24. A brief history (time line) 1839 Schleiden & Schwann Cell theory 1859Darwin: <<Origin of Species>>1865Mendel: Genetics1869Miescher: discovered DNA1902 Sutten Chromosome 1910,1916 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 used plasmid to clone DNA1977 Gilbert & Sanger: sequence 1986 Mullis: PCR1990 Watson et al: Lauched the HGP1997 Wilmut: Dolly 1998- Bioinformatics,Proteomes(ome) 遗传学与分子生物学系

  25. Major Achievements of Molecular Biology after 70s • DNA polymerase dependent on RNA (Reverse transcription) • Tool enzymes (restrictive endonuclease, DNA ligase, etc) • Split gene • DNA Sequencing • MAb • Ribozymes • PCR • Gene regulation • Transgenic organism • DNA recombination in intro and in vivo (gene therapy) • HGP • iRNA • Proteomics • Hapmap (SNPs) • Bioinformatics • Systems biology 遗传学与分子生物学系

  26. Lecture I: Introduction Of Molecular Biology • Definition, Goal and Scope • Fundamentals • A brief history • Methodology of Molecular Biology • Role in Medical sciences • prospective 遗传学与分子生物学系

  27. Physical and chemical approaches _________________________________________________________ Ultracentrifuge* 20s Size and shape of molecule in centrifugal field Electrophoresis* 30s separation of protein and nucleic acids based on size and/or charge in electric field Electron Microscope 30s directly visualization of cellar ultra- structure, including DNA Radioisotope tracers* 40s tracking flow of molecule through a metabolic pathway X-ray diffraction* 50s provides precise measurement of 3- D structure of protein and nucleic acid Amino acid analysis* 50s determination of order of amino acid in protein Nucleic acid hybridization 60s quantitative assessment of similarity of RNAs or DNAs Recombinant DNA * 70s genetic engineering of novel genes ------------------------------------------------------------------------------------------------ * Denotes associated with Nobel Prize 遗传学与分子生物学系

  28. Genetic Methods • Mutant organisms • recoginize a Novel process • unravel a comlex metabolic pathway • establish a relationship between an identified gene and its previous unknown function • Pure genes • pin-point substitution or deletion • reverse genetics 遗传学与分子生物学系

  29. Model Biological system Virus Bacteria Bacteriophage Yeast Worm (C. elegant) Plant (Arabidopsis) Fly Mouse Rat human 遗传学与分子生物学系

  30. Logic of molecular biology • The efficiency argument • Phylogenetic history • Quantitative assessment • Model building • Parallelism • Strong inference • Optimism 遗传学与分子生物学系

  31. Lecture I: Introduction Of Molecular Biology • Definition, Goal and Scope • Fundamentals • A brief history • Methodology of Molecular Biology • Role in Medical sciences • prospective 遗传学与分子生物学系

  32. Molecular medicine Molecular immunologyMolecular pharmacologyMolecular pathologyMolecular entomologyMolucular MicrobiologyMolecular taxanomyMolecular biomathmatics Bioinformatics 遗传学与分子生物学系

  33. 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

  34. 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

  35. 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

  36. 基因诊断技术 • PCR技术 • 核酸探针杂交技术 • 基因芯片(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 :“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

  37. 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

  38. 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

  39. 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

  40. 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

  41. 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

  42. 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

  43. 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

  44. Lecture I: Introduction Of Molecular Biology • Definition, Goal and Scope • Fundamentals • A brief history • Methodology of Molecular Biology • Role in Medical sciences • prospective 遗传学与分子生物学系

  45. 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、细胞,确立或发现500种人类新型蛋白质并探索其表达规律和作用网络 发现重大疾病如肝炎、肝癌、心血管病相关的蛋白质群,为防治提供新的预警、诊断标志和药物靶标。 遗传学与分子生物学系

  46. 人类蛋白质组正式启动 • 2001年成立国际人类蛋白质组组织(HUPO),2003.12.15启动两个首批行动计划。 • 人类肝脏蛋白质组计划(HLPP)由中国军事医学科学院副院长贺福初院士领导,16国80多个实验室参加。中国第一次领导重大国际协作计划。 • 人类血浆蛋白质组计划(HPPP)由美国科学家牵头,13国47个实验室参加。 • 第三届国际人类蛋白质组大会今年在北京举行。主题:蛋白质组-生命真谛的诠释。 遗传学与分子生物学系

  47. 蛋白质组研究技术 • 2D-MS • 酵母双杂交系统 • 噬菌体展示技术 • 蛋白质微阵列 • 大规模数据处理的计算机系统和软件 遗传学与分子生物学系

  48. 蛋白质组研究步骤 • 2-D电泳 • 双向高效柱层析分离蛋白质 • 氨基酸组成分析、C-端或N-端氨基酸序列分析及MS鉴定所分离的蛋白质 • 生物信息学数据库对鉴定结果进行存储、处理、对比和分析。 遗传学与分子生物学系

  49. RNAi 核糖核酸介入(RNAi) 医生们也许可关闭在人体中引发癌症、HIV、埃博拉病毒的基因 也许能和早期抗生素相比,21世纪医药产生革命性变化 遗传学与分子生物学系