遗传学与分子生物学系.ppt

遗传学与分子生物学系,Molucular Biology Lu Shermin (吕社民) Tel: 82657764 Email:lushemin,遗传学与分子生物学系,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,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 disciplines of genetics and biochemistry. Hybrid discipline Biochemistry Genetics Molecular Biology Biophysics,遗传学与分子生物学系,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,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,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,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,遗传学与分子生物学系,“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,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,Nucleotides,Base Sugar (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 Biology,Definition, Goal and Scope Fundamentals A brief history Methodology of Molecular Biology Role in Medical sciences prospective,Gregor 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 Mendel: Genetics 1869 Miescher: discovered DNA 1902 Sutten Chromosome 1910,1916 Morgan: gene are on chromosomes 1944 Avery: identified DNA as the material genes are made of 1953 Watson Crick： DNA structure 1958 Meselson & Stahl: semiconservative replication of DNA 1961 Jacob et al: discovered mRNA 1972 Berg: recombinant DNA in vitro 1973 Cohen: first used plasmid to clone DNA 1977 Gilbert & Sanger: sequence 1986 Mullis: PCR 1990 Watson et al: Lauched the HGP 1997 Wilmut: Dolly 1998- Bioinformatics,Proteomes(ome),遗传学与分子生物学系,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,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,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,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,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,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,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,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、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(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,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 Biology,Definition, Goal and Scope Fundamentals A brief history Methodology of Molecular Biology Role in Medical sciences prospective,遗