0901第00章分生绪论第一次课

1、1医学分子生物学医学分子生物学 medical molecular biologyhonghua zhengdepartment of biochemistry & molecular biologytel:-mail: 2 医学分子生物学医学分子生物学人民卫生出版社，药立波主编人民卫生出版社，药立波主编 molecular biology， robert f.weaver, mcgraw-hill companies, inc. ，2000（影印版，（影印版，科学出版社）科学出版社） 现代分子生物学现代分子生物学（第二版），朱玉贤、李毅编（第二版），朱玉贤、

2、李毅编著，高等教育出版社，著，高等教育出版社，2002reference books3 the greatest intellectual revolution of the last 40 years may have taken place in biology.can anyone be considered educated today who does not understand a little about molecular biology? -f.h.westheimer4 the relationship between biochemistry and molecular

3、 biology biochemistry major in biological phenomena from the chemistry angle, especially on the structure and metabolism changes of the various living creature molecules. molecular biology emphasizes the essence of the life-mainly research the structure and function of huge molecules (nucleic acid a

4、nd protein), delivering and regulation of gene information.5i. whats medical molecular biology?introductionii. the contents of medical molecular biology6i. whats medical molecular biology?7 the molecular biology is science that researches biological phenomena, life essence and life activity and its

5、law at the molecular level. it is an theory and technique system formed at the molecular level, which is called molecular biology. the birth of molecular biology can match with the discovery of cell and the establishing of theory of evolution . it is one of the greatness achievements of natural scie

6、nce in 20th century.1. molecular biology82. medical molecular biology medical science molecular biology researches the life activity and its law under the normal and abnormal condition of human. it studies the prevention, diagnosis and cure of human diseases from the molecule horizontal. the basic m

7、edical science is the foundation of the whole medical science, while the medical molecular biology links the basic medical science and its each sub-branch with clinical medical science like a string .9ii. the contents of medical molecular biology?10 1112in 1865, gregor mendel published mendelian inh

8、eritance (孟德尔遗传定律孟德尔遗传定律 ).garden peainheritance occurred through blending of each trait of the parents in the offspring. inheritance is particulate（微粒，微粒（微粒，微粒的）的）. each parent contributes particles, or genetic units, to the offspring.1822-1884/rc/ab/bc/gregor_mendel.h

9、tmlgregor mendelin 1910, thomas hunt morganprovided the first definitive evidence for the chromosome theory of inheritance 1933 nobel prize in physiology/ medicine for his discoveries concerning the role played by the chromosome in heredity（遗传）, demonstrated that genes are on the chromosome“.fruit f

10、ly ( drosophia melanogaster ) 1866-1945/scientists/morgan.htmthe discovery of dna1869, friedrich miescher discovered nuclein and the major component of nuclein is dna. 1844-1895http:/www.fmi.ch/members/marilyn.vaccaro/ewww/index2.htmlthe composition of genes1944, oswald avery

11、 demonstrated that the chromosome is composed of dna.not rna or protein ! frederick griffith 肺炎球菌转化试验肺炎球菌转化试验1877-1955/dnaftb/concept_17/con17bio.htmlthe discovery of dna1869, friedrich miescher discovered nuclein and the major component of nuclein is dna. 1844-1895http:/www.fmi.

12、ch/members/marilyn.vaccaro/ewww/index2.htmlrosalind frankin(核与磷酸连接成的扭曲绳子，每一节上都有配对的碱基)1951. kings lab. london university ukm. h. f. wilkinsxray photograph of dna with high qualityjames watson (34y)francis crick (46y)maurice wilkins (46y)1962 nobel prizein the early 1960smarshall nirenberggobind khora

13、na robert w. holley1968 nobel prize in medicine1927-1922-1922-for their interpretation of the genetic code and its function in protein synthesis.1975. howard howard temintemin (41y)david baltimore david baltimore (37y)reverse transcription（引发癌症的内因）（引发癌症的内因）22one gene-one enzymebeadle tatum 23桑格桑格 sa

14、nger 吉尔伯特吉尔伯特 gilbert 伯格伯格 berg 1980 sanger （英）（英） gilbert & berg（英）（英）酶法核苷酸测酶法核苷酸测序的设计者序的设计者化学测序法的设计者化学测序法的设计者dnadna重组，在细菌中表重组，在细菌中表达胰岛素达胰岛素dnadna重组技术的元老重组技术的元老sanger还由于测定了牛胰岛素的一级结构而获得还由于测定了牛胰岛素的一级结构而获得1958年诺贝尔化学奖。年诺贝尔化学奖。24 1989 altman （加）（加） cech（美）（美）founder of ribozyme（核酶核酶）sidney altman th

15、omas r. cech the nobel prize in chemistry 1980“for their contributions concerning the determination of base sequences in nucleic acidswalter gilbert frederick sanger 1932-1918-1983. barbara mcclintockbarbara mcclintock (86y)dna transposable elementthe nobel prize in chemistry 1989“ror their discover

16、y of catalytic properties of rna ribozymesidney altman thomas r. cechyale university new haven, ct, usa university of colorado boulder, co, usa1939 -1947- the nobel prize in chemistry 1993kary b. mullis 1944 -“for his invention of the polymerase chain reaction (pcr) method1997，the nobel prize in phy

17、siology or medicine “for his discovery of prions a new biological principle of infectionstanley b. prusiner univ. of california,school of medicine usa 1942 -293031 two major directions of the current medical molecular biology:（1） constantly put the theory and techniques deepen.（2） kept touch with an

18、d integrate with other subjects.32the four frontier research fields at present（1） structural molecular biology（2） human genomic project（3）gene expression and regulation（4）signal transduction33（1） structural molecular biology biological function depends on the structure. only biomacromolecules have a

19、 specific space solid structure ,namely three dimensional structure ,can they have physical capabilities. 34 （2） human genomic project the human genome project (hgp) is an international scientific research project with a primary goal of determining the sequence of chemical base pairs which make up d

20、na, and of identifying and mapping the approximately 20,00025,000 genes of the human genome from both a physical and functional standpoint.35 post-genomics includes: 1） functional genomics 2） proteomics 3） comparative genomics 4）cells plan 5） bioinformatics and biochip36 （3） gene expression and regu

21、latory research gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. these products are often proteins, but in non-protein coding genes such as ribosomal rna (rrna), transfer rna (trna) or small nuclear rna (snrna) genes, the product

22、is a functional rna.37 （4） signal transduction signal transduction is the process by which an extracellular signaling molecule activates a membrane receptor, that in turn alters intracellular molecules creating a response. there are two stages in this process: a signalling molecule activates a certa

23、in receptor on the cell membrane, causing a second messenger to continue the signal into the cell and elicit a physiological response. in either step, the signal can be amplified, meaning that one signaling molecule can cause many responses.3839401. applied in medical basic theory research 2. applie

24、d in gene diagnosis3. applied in gene therapy4. applied in bioengineering and biopharmaceuticals5. applied in preventive medicine411. the basis of cell molecular biologythe cell is the structural and functional basic unit of life. so cell molecular biologys research is omnibearing, but on the whole

25、it comes down to two aspects:1)how gene and gene products control cells important life activities, such as growth, differentiation, decrepitude and so on.2)how gene products and other biomolecules assemble highly organized cell structures and make cells carry on ordered life activities. 42 gene diag

26、nosis is the detection of genetic disorders by dna analysis. new gene diagnosis methods make it possible to find the chromosomal location of genes that are responsible for neurological and psychiatric conditions and to identify structural changes in these genes that are responsible for causing disea

27、se. this information can be quite useful for identifying individuals that carry faulty genes. 2. gene diagnosis43（1）diagnose genetic diseases by medical molecular biology technology, pcr or southern blot.（2）diagnose infectious diseases by molecular hybridization and pcr.（3） detect point mutation of

28、oncogene and anti-oncogene by applying pcr/aso or pcr-sscp, you can detect point mutation of oncogene and anti-oncogene.（4） carry on medicolegal expertise by southern blot and genetic chip.44 with the development of gene therapy basic research, now gene therapy is not only applied in single-gene gen

29、etic diseases , but also some polygene genetic diseases, for example : polygenetic diseases malignant tumor some infectious diseases, such as aids cardiovascular diseases45 截止到2002年底，全世界批准的基因治疗临床试验方案达到了636个，病人数量3 496个。在所批准的基因治疗临床试验方案中，美国占了大多数，共有505个，占了总数的79.4%；其次是欧洲103个，占总数的16.2%；亚洲共有9个，仅占总数的1.4%。47transgenic animalstransgeni