1、遺傳學與分子生物學系molucular biologylu shermin (呂社民)tel: 82657764email:遺傳學與分子生物學系lecture i: introduction of molecular biology1. definition, goal and scope2. fundamentals3. a brief history4. methodology of molecular biology5. role in medical sciences6. prospective遺傳學與分子生物學系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 遺傳學與分子生物學系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遺傳學與分子生物學系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遺傳學與分子生物學系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遺傳學與分子生物學系lecture i: introduction of molecular biology1. definition, goal and scope2. fundamentals3. a brief history4. methodology of molecular biology5. role in medical sciences6. prospective遺傳學與分子生物學系遺傳學與分子生物學系“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遺傳學與分子生物學系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遺傳學與分子生物學系nucleotides base sugar

9、(base + sugar = nucleoside) phosphate (nucleoside + phosphate = nucleotide)遺傳學與分子生物學系遺傳學與分子生物學系遺傳學與分子生物學系遺傳學與分子生物學系遺傳學與分子生物學系遺傳學與分子生物學系遺傳學與分子生物學系遺傳學與分子生物學系遺傳學與分子生物學系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)遺傳學與分子生物學系a brief history (time line) 1839 schleiden & schwann cell theory 1859 darwin:1865 mendel:

11、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: recombina

12、nt 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)遺傳學與分子生物學系major achievements of molecular biology after 70sdna polymerase dependent on rna (reverse transcrip

13、tion)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遺傳學與分子生物學系lecture i: introduction of molecular biolog

14、y1. definition, goal and scope2. fundamentals3. a brief history4. methodology of molecular biology5. role in medical sciences6. prospective遺傳學與分子生物學系physical and chemical approaches_ultracentrifuge*20ssize and shape of molecule in centrifugal fieldelectrophoresis* 30s separation of protein and nucle

15、ic 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 protein and nu

16、cleic 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遺傳學與分子生物學系genetic methodsmutant organisms re

17、coginize 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遺傳學與分子生物學系model biological systemvirusbacteriabacteriophageyeastworm (c. elegant)plant (arabi

18、dopsis)flymouserathuman遺傳學與分子生物學系logic of molecular biologythe efficiency argumentphylogenetic historyquantitative assessmentmodel buildingparallelismstrong inferenceoptimism遺傳學與分子生物學系lecture i: introduction of molecular biology1. definition, goal and scope2. fundamentals3. a brief history4. methodo

19、logy of molecular biology5. role in medical sciences6. prospective遺傳學與分子生物學系 molecular medicine molecular immunology molecular pharmacology molecular pathology molecular entomology molucular microbiology molecular taxanomy molecular biomathmatics bioinformatics遺傳學與分子生物學系發育、分化與衰老細胞增殖調控神徑、內分泌和免疫調控致病基因

20、和易感基因的鑒定和克隆遺傳學與分子生物學系 腦和神經生物學神經系統發育、信號傳遞：最富挑戰性、最復 雜的問題之一。腦約有3萬個基因處于表達狀態 分子水平揭示腦的思維、記憶和學習等功能治療精神病 遺傳學與分子生物學系基因診斷 特異性強、靈敏度高、簡便快速。遺傳病（優生優育）傳染病(包括hiv) 現已發展到對一些常見病 (如糖尿病、動脈粥樣硬化及精神分裂癥等)的診斷，還應用于結核病、肝炎、傳染病及惡性腫瘤的診斷及法醫學鑒定。 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行分子診斷試驗的設計。 遺傳學與分子生物學系基因診斷技術 pcr技術 核酸探針雜交技術 基因芯片(gene chip)技

21、術 限制性片段長度多態性(rflp) 單核苷酸多態性(snp) 發展趨勢發展趨勢 ：“自動化”、“程序化”、“非標記技術”和“多病種”等特色 。遺傳學與分子生物學系基因治療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 遺傳學與分子生物學系基因治療希望與局限（1）基因治療癌癥未獲進展（2）僅限于治療少數疾病，費用昂貴（3）導入人體的目的基因表達水平（4）獲得長期表達效果難遺傳學與

22、分子生物學系在中藥學中的應用 蛋白質或酶技術 核酸技術：藥用植物鑒別、rflp、rapd、dna footprinting、biochip 藥用植物育種 藥用植物次生代謝產物遺傳學與分子生物學系生物制藥 按生物化學性質分為：氨基酸類、有機酸、醇酮類、維生素、酶及輔酶類、脂類、多肽和蛋白質類、核酸類及其衍生物、多糖等。 按生物工程學科分為：基因工程制藥(上百種多肽藥物)、細胞工程制藥、微生物工程制藥和酶工程制藥四大類。 轉基因的動植物 遺傳學與分子生物學系生物制藥發展趨勢1、動物細胞高效表達和細胞大量培養。 2、蛋白質工程和蛋白質雜交研究。 3、藥物劑型研究。 4、藥物配伍研究。 5、基礎醫學的

23、生物技術研究。 6、研究開發第二代生物技術藥物，即核 酸、糖、脂類三類藥物。 遺傳學與分子生物學系疫苗研制 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 、結核病dna疫苗 、瘧疾dna疫苗 遺傳學與分子生物學系環境監測與凈化基因探針：飲用水，6000兒童/天死“超級菌”、 “超級質粒”：辛烷、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、農藥和殺蟲劑 遺傳學與分子生物學系lecture i: introduction of molecular biology1. definition, goal and scope2. fundamentals3. a brief history4. methodology of molecular biology5. role in medical sciences6