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1、 Molecular biology Lesson programContents Period Introduction 2 Cell and biological macromolecules 6 DNA damage,repair,recombination and transposition 6Research methods commonly used 12Gene transcription and regulation 12 RNA processing and RNPs 4Genetic codons and tRNA 2Protein synthesis 4 Totally

2、48Central dogmaResearch levelnEcosystemnPopulationnIndividualnSystemnOrgannTissuenCellnMolecule Schematic relationship between biochemistry, genetics and molecular biologyDefinition Molecular biology seeks to explain the relationships between the structure and function of biological molecules and ho

3、w these relationships contribute to the operation and control of biochemical processes. TextbooksExample My research activities - Molecular Biology - Microbiology - Environmental medicine A brief history of Molecular biologyBig namesnCharles Darwin (1809-1882)nWho am I?nWhere am I from? On the origi

4、n of species by means of the natural selection (1859)Cell theorynAntony van Leeuwenhoek (1632-1723) - microscopenRobert Hooke (1635-1703) - cellnTheodor Schwann (1810-1882) - animal cellnMatthias Schleiden (1804-1881) - plant cellClassical geneticsGregor Mendel 1822-1884Thomas Hunt Morgan 1866-1945

5、Nobel prize (1933)Molecular geneticsThe discovery of DNA 1869, Friedrich MiescherThe composition of genes 1944, AveryThe relationship between genes and proteins1941, George Beadle & EL TatumOswald Avery (1877-1955)Great job, Not Nobel Prize winnerMartha Chase (1930- ) and Alfred Hershey (1908 19

6、97,Nobel Prize winner in 1969)Cold Spring Harbor Laboratory, 1953 Activities of genes- How genes are replicated 1953, J Waston, F Crick. 1958, M Meselson, F Stahl- How genes direct the production of polypeptides 1966, M Nirenberg, HG Khorana- How genes accumulate mutations- Gene cloningJames Waston(

7、1928-)Francis Crick(1916-2004)Nobel Prize winnersin 1962 Molecular biology time line1859 Charles Darwin Published On the Origin of Species1865 Gregor Mendel Advanced the principles of segregation and independent assortment1869 Friedrich Miescher Discovered DNA1900 HD Vries, C Correns Rediscovered Me

8、ndels principles EV Tschemak1902 Archibald Garrod Noted the first genetic disease1902 W Sutton, T Boveri Proposed the chromosome theory1908 GH Hardy Formulated the Hardy-Weinberg W Weinberg principle1910 Thomas Hunt Morgan Demonstrated that genes are on 1916 Calvin Bridges chromosome1913 AH Sturteva

9、nt Constructed a genetic map1927 HJ Muller Induced mutation by X-rays1931 Harriet Creighton, Obtained physical evidence for Barbara McClintock recombination1941 G Beadle, EL Tatum Proposed the one gene-one enzyme hypothesis1944 O Avery, C Mcleod Identified DNA as the material M McCarty genes are mad

10、e of1953 J Waston, F Crick Determined the structure of DNA R Franklin, M Wilkins1958 Matthew Meselson, Demonstrated the semiconservative Franklin Stahl replication of DNA1961 S Brenner, F Jacob Discovered messenger RNA M Meselson1966 Marshall Nirenberg Finished unraveling the genetic code Har Gobind

11、 Khorana1972 Paul Berg Made the first recombination DNA in vitro1973 H Boyer, S Cohen First used a plasmid to clone DNA1977 W Gilbert, F Sanger Worked out methods to determine the sequence of bases in DNA1977 Frederick Sanger Determined the base sequence of an entire viral genome (174)1977 P Sharp,

12、R Roberts Discovered introns in genes1990 LC Tsui, F Collins, Found the gene that is responsible for J Riordan cystic fibrosis1990 J Waston and others Launched the Human Genome Project to map the entire human genome and, ultimately to determine its base sequence1991 WF Anderson First successful gene

13、 therapy performed and others on two girls with severe combined immunodeficiency,bubble-boy syndrome1993 The Huntingtons Identified the Huntingtons disease gene Disease Group 1995 Craig Venter Determined the base sequences of the Hamilton Smith genomes of two bacteria1996 Many investigators Determin

14、ed the base sequence of the genome of one yeast 1997 F Blattner, Determined the base sequence of the T Horiuchi, genome of Escherichia coli and others1997 Ian Wilmut and others Cloned a sheep (Dolly) from an adult udder cell1998 The genome of Caenerhabditis elegans, a small soil nematode, was comple

15、tely sequenced (97Mb)1999 Drosophila melanogaster (fruitfly) genome completely sequenced (175 Mb)2000 Completion of the Arabidopsis thaliana sequence (157 Mb) Human genome draft version finished (3200 Mb)2002 Presentation of human genome by Celera Genomics and the collaborating group of laboratories

16、 supported by public foundationNow RNAi, epigenetics, proteomics 2007, Jame waston, first personnel genome 2007, skin cell to stem cell1990-19991990 - Joseph E. Murray and E. Donnall Thomas, United States, for their discoveries about organ and cell transplantation in the treatment of disease1991 - E

17、rwin Neher and Bert Sakmann, Federal Republic of Germany, for finding what single ion channels do in cells 1992 - Edmond H. Fischer, Switzerland and the United States, and Edwin G. Krebs, United States, for finding reversible protein phosphorylation as a biological control mechanism1993 - Richard J.

18、 Roberts, United Kingdom, and Phillip A. Sharp, United States, for their discoveries of split genes1994 - Alfred G. Gilman, and Martin Rodbell, United States, for finding G-proteins and the role of these proteins in signal transduction in cells1995 - Edward B. Lewis, United States, Christiane Nsslei

19、n-Volhard, Federal Republic of Germany, and Eric F. Wieschaus, United States, for finding how embryonic development is changed by genes1996 - Peter C. Doherty, Australia, and Rolf M. Zinkernagel, Switzerland, for finding how the immune system knows which cells are virus-infected1997 - Stanley B. Pru

20、siner, United States, for his discovery of Prions, proteins that make people sick1998 - Robert F. Furchgott, Louis J. Ignarro and Ferid Murad, United States, for finding how nitric oxide works as a signalling molecule in the cardiovascular system1999 - Gnter Blobel, United States, for the discovery

21、that proteins have built-in signals that control their transport and localization in the cellNobel Prize in Physiology and Medicine2000-20092000 - Arvid Carlsson, Sweden, Paul Greengard, United States, and Eric R. Kandel, United States, for their discoveries about signal transduction in the nervous

22、system 2001 - Leland H. Hartwell, United States, Tim Hunt, United Kingdom, and Sir Paul M. Nurse, United Kingdom, for finding the main controls in the cell cycle2002 - Sydney Brenner, United Kingdom, H. Robert Horvitz, United States, and John E. Sulston, United Kingdom, for their finding the genetic

23、 controls of organ development and programmed cell death 2003 - Paul Lauterbur, United States, and Sir Peter Mansfield, United Kingdom, for inventing magnetic resonance imaging2004 - Richard Axel and Linda B. Buck, United States, for finding odorant receptors and the organization of the olfactory sy

24、stem, (how we smell things)2005 - Barry J. Marshall and J. Robin Warren, Australia, for finding the bacterium Helicobacter pylori that causes gastritis and peptic ulcer disease2006 - Andrew Z. Fire and Craig C. Mello, United States, for finding how RNA interference can switch genes on or off2007 - M

25、ario R. Capecchi, United States, Sir Martin J. Evans, United Kingdom, Oliver Smithies, United States, for finding how to change genes in mice by the use of embryonic stem cells2008 - Harald zur Hausen, Germany, for finding the human papilloma viruses causing cervical cancer2008 - Franoise Barr-Sinou

26、ssi and Luc Montagnier, France, for finding the human immunodeficiency virus2009 - Elizabeth H. Blackburn , Carol W. Greider , Jack W. Szostak ,USA, for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase Nobel Prize in Chemistry (Biochemistry)(1980-now)1980 Paul Be

27、rg (USA, *1926-06-30) Studies on the biochemistry of nucleic acids, particularly hybrid DNA (technology of gene surgery) Walter Gilbert (USA, *1932-03-21) Frederick Sanger (United Kingdom, 1918-08-13) Determination of base sequences in nucleic acids 1982 Aaron Klug (United Kingdom, *1926-08-11) Deve

28、lopment of crystallographic methods for the elucidation of biologically important nucleic acid protein complexes 1984 Robert Bruce Merrifield (USA, 1921-07-15 - 2006-05-14) Method for the preparation of peptides and proteins 1988 Johann Deisenhofer (Germany, *1943-09-30) Robert Huber (Germany, *1937

29、-02-20) Hartmut Michel (Germany, *1948-07-18) Determination of the three-dimensional structure of a photosynthetic reaction center 1989 Sidney Altman (Canada, *1939-05-08) Thomas Robert Cech (USA, *1947-12-08) Discovery of the catalytic properties of ribonucleic acid (RNA)1993 Kary Banks Mullis (USA

30、, *1944) Invention of the polymerase chain reaction (PCR) Michael Smith (Canada, *1932) Development of site specific mutagenesis 1997 Paul D. Boyer (USA, *1918) John E. Walker (United Kingdom, *1941) for their elucidation of the enzymatic mechanism underlying the synthesis of adenosine triphosphate

31、(ATP) Jens C. Skou (Denmark, *1918) for the first discovery of an ion-transporting enzyme, Na+, K+-ATPase 2002 John B. Fenn (USA, *1917) Koichi Tanaka (Japan, *1959) for their development of soft desorption ionisation methods for mass spectrometric analyses of biological macromolecules Kurt Wthrich (Switzerland, *1938) for his development of nuclear magnetic resonance spectroscopy for determining the three-dimensional structure of biological macromolecules in solution 2003 Peter Agre (USA, *1949) for the dis

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