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    现在位置时时彩网络平台>技术资料首页>实验室信息>实验室介绍>英国桑格研究院(Sanger Institute)

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    英国桑格研究院(Wellcome Trust  Sanger Institute) www.sanger.ac.uk
    英国桑格研究院(Sanger Institute)
    位于剑桥的桑格研究院(Sanger Institute),是世界上最重要的生物技术研发中心之一,同时也是将基因研究转化为商业用途的重要基地,目前人类基因研究项目正在该研究院进行。

    弗雷德里克·桑格(1918年8月13日-),OM,CH,CBE,FRS(Frederick Sanger,1918年8月13日-)是一位英国生物化学家,曾经在1958年及1980年两度获得诺贝尔化学奖,是第四位两度获得诺贝尔奖,以及唯一获得两次化学奖的人。
    弗雷德里克·桑格 Frederick Sanger
    早年
    桑格于1918年8月13日出生于英国格洛斯特郡,父亲是一位医生。从布莱恩斯滕高中(Bryanston School)毕业后,桑格进入了剑桥大学圣约翰学院,并于1939年完成自然科学文学士学位。他原本打算研究医学,但后来转而对生物化学感兴趣,而剑桥在当时也正好有许多早期的生物化学先驱。桑格在1943年获得哲学博士学位。他在1940年时与玛格丽特·琼·豪(Margaret Joan Howe)结婚,他们育有两个儿子和一个女儿。

     
    蛋白质与DNA序列研究
    桑格在1955年将胰岛素的胺基酸序列完整地定序出来,同时证明蛋白质具有明确构造。他利用自己新发现的桑格试剂[1],也就是2,4-二硝基氟苯(2,4-dinitrofluorobenzene)将胰岛素降解成小片段,并与专门水解蛋白质的胰蛋白酶混合在一起。再将一部分混合物的样本置放于滤纸的一面,并利用一种色层分析方法来做进一步的实验,首先他将一种溶剂从单一方向通过滤纸,同时又让电流以相反向通过。

    由于不同的蛋白质片段有不同的溶解度与电荷,因此在电泳后,这些片段最后会各自停留在不同的位置,产生特定的图案。桑格将此图案称为「指纹」;不同的蛋白质拥有不同的图案,成为可供辨识且可重现的特征。之后桑格又将小片段从新组合成胺基酸长链,进而推导出完整的胰岛素结构。因此得出结论,认为胰岛素具有特定的胺基酸序列。这项研究使他单独获得了1958年的诺贝尔化学奖。

    1975年时,桑格发展出一种称为链终止法(chain termination method)的技术来测定DNA序列,这种方法也称做「双去氧终止法」(Dideoxy termination method)或是「桑格法」[2]。两年之后,他利用此技术成功定序出Φ-X174噬菌体(Phage Φ-X174)的基因组序列。这也是首次完整的基因组定序工作。他所发明的技术比起当时其他方法使用了较不具毒性的材料。主要是先进行PCR,利用DNA引子和DNA聚合酶使DNA链得以展开复制,再利用双去氧核苷酸(dideoxynucleotides)来终止DNA链的合成。实验会使不同序列的DNA带有不同长度,使其得以经由电泳来做分析。

    这项研究后来成为人类基因组计画等研究得以展开的关键之一,并使桑格于1980年再度获得诺贝尔化学奖,与桑格合作研究的沃特·吉尔伯特,以及另一团队的保罗·伯格(Paul Berg)也一同获奖。第二座诺贝尔奖使他成为继玛莉·居礼、莱纳斯·鲍林,以及约翰·巴丁之后的第四位两度获奖者。到了1979年,桑格又与吉尔伯特和伯格一同获得哥伦比亚大学的路易莎·格罗斯·霍维茨奖(Louisa Gross Horwitz Prize)。

     
    近年影响
    桑格于1982年退休,英国的维康信托基金会(Wellcome Trust)和医学研究理事会(Medical Research Council),于1993年成立了桑格中心(Sanger Centre)[3],这座研究机构现在称为桑格研究院(Sanger Institute),地点位于英国剑桥,是世界上进行基因组研究的主要机构之一。 2007年,维康信托提供英国生物化学学会(British Biochemical Society)一项补助,使其为桑格从1989年以后的实验研究纪录进行建档及保存。

     其他名誉及头衔
    1954年成为皇家学会会员(FRS)。
    1963年获得英帝国司令勋章(CBE)。
    1981年获得名誉勋位(CH)。
    1986年获得功绩勋章(OM)。



    Frederick Sanger, OM, CH, CBE, FRS (born 13 August 1918) is an English biochemist and twice a Nobel laureate in chemistry. He is the fourth (and only living) person to have been awarded two Nobel Prizes.

    Contents [hide]
    1 Early years
    2 Research
    3 Later life
    4 Awards and honours
    5 References
    6 Books containing references to Fred Sanger
    7 External links
     

     Early years
    Sanger was born in Rendcomb, a small village in Gloucestershire, the second son of Frederick Sanger, a medical practitioner, and his wife, Cicely. He was born on August 13, 1918, and educated at The Downs School (Herefordshire) and Bryanston School and then completed his Bachelor of Arts in natural sciences from St John's College, Cambridge in 1939. Raised as a Quaker, he learned to abhor violence, and during the Second World War he was a conscientious objector, being allowed to continue his research for a Ph.D.

    He originally intended to study medicine, but became interested in biochemistry; some of the leading biochemists in the world were at Cambridge at the time. He completed his Ph.D. in 1943 under A. Neuberger, on lysine metabolism and a more practical problem concerning the nitrogen of potatoes.

     Research
    Sanger's first triumph was to determine the complete amino acid sequence of the two polypeptide chains of insulin in 1955.[citation needed]. Prior to this it was widely assumed that proteins were somewhat amorphous. In determining these sequences, Sanger proved that proteins have a defined chemical composition. For this purpose he used the "Sanger Reagent", fluorodinitrobenzene (FDNB), to react with the exposed amino groups in the protein and in particular with the N-terminal amino group at one end of the polypeptide chain. He then partially hydrolysed the insulin into short peptides (either with hydrochloric acid or using an enzyme such as trypsin). The mixture of peptides was fractionated in two dimensions on a sheet of filter paper: first by electrophoresis in one dimension and then, perpendicular to that, by chromatography in the other. The different peptide fragments of insulin, detected with ninhydrin, moved to different positions on the paper, creating a distinct pattern which Sanger called “fingerprints”. The peptide from the N-terminus could be recognised by the yellow colour imparted by the FDNB label and the identity of the labelled amino acid at the end of the peptide determined by complete acid hydrolysis and discovering which dinitrophenyl-amino acid was there. By repeating this type of procedure Sanger was able to determine the sequences of the many peptides generated using different methods for the initial partial hydrolysis. These could then be assembled into the longer sequences to deduce the complete structure of insulin. Sanger's principal conclusion was that the two polypeptide chains of the protein insulin had precise amino acid sequences and, by extension, that every protein had a unique sequence. It was this achievement that earned him his first Nobel prize in Chemistry in 1958. This discovery was crucial for the later sequence hypothesis of Crick for developing ideas of how DNA codes for proteins.

    In the 1960s he turned his attention to RNA molecules and again developed methods for separating fragments of these generated with specific nucleases. In the course of this he discovered in 1964, with Kjeld Marcker, the formylmethionine tRNA which initiates protein synthesis (in bacteria; this is closely related to the initiator methionine tRNA which was later discovered in eukaryotes). By 1967 he had determined the nucleotide sequence of the 5S ribosomal RNA from Escherichia coli, a small RNA about 115 nucleotides long. He then turned to DNA and, by 1975, had developed the “dideoxy” method for sequencing DNA molecules, also known as the Sanger method.[1] Two years later Sanger used his technique to successfully sequence the genome of the Phage Φ-X174; the first fully sequenced DNA-based genome. He did this entirely by hand. This has been of key importance in such projects as the Human Genome Project and earned him his second Nobel prize in Chemistry in 1980, which he shared with Walter Gilbert and Paul Berg. He is thus far (2009) the only person to have been awarded two Nobel Prizes in Chemistry, and one of only four two-time Nobel laureates: the other three were Marie Curie (Physics, 1903 and Chemistry, 1911), Linus Pauling (Chemistry, 1954 and Peace, 1962) and John Bardeen (twice Physics, 1956 and 1972). In 1979, he was awarded the Louisa Gross Horwitz Prize from Columbia University together with Walter Gilbert and Paul Berg.

    Sanger's techniques used random distributions to get ordered sequence. The homochromatography was made from randomized RNA polymers. The plus-minus sequencing system used the random termination of polymerase to get a population of DNA polymers of each size. The dideoxy system took advantage of the random insertion of dideoxy nucleotides at every sequence position. The ordering of the phi X 174 genome used random shot-gun sequencing (later employed by Venter) and then closing the sequence circle by computer alignment. Professor Pieczenik used Sanger logic i.e. random distribution of nucleotides to create the first combinatorial libraries of peptides. //www2.mrc-lmb.cam.ac.uk/archive/g_pieczenik.html

      Later life
    Sanger retired in 1983 to his home, “Far Leys”, in Swaffham Bulbeck outside Cambridge where he became an avid gardener. Adjacent to his extensive garden is “Sanger Wood”. In 1992, the Wellcome Trust and the Medical Research Council founded the Sanger Centre (now the Sanger Institute), named after him. The Sanger Institute, located near Cambridge, England, is one of the world's most important centres for genome research and played a prominent role in sequencing the human genome.

    Almost his only public utterance in two decades was to put his name to a letter by other UK Nobel laureates protesting about the Iraq war. Referring to his youthful conscientious objection, he said, "I still hate war. That is why I signed that letter".

    In 2007 the British Biochemical Society was given a grant by the Wellcome Trust to catalogue and preserve the 35 laboratory notebooks in which Sanger recorded his remarkable research from 1944 to 1983. In reporting this matter, Science magazine noted that Sanger, "the most self-effacing person you could hope to meet", now was spending his time gardening at his Cambridgeshire home.[2]

    Even in retirement Sanger has used his extensive knowledge of DNA to aid modern scientists and academics in their work.

     Awards and honours
    This section may require cleanup to meet Wikipedia's quality standards. Please improve this section if you can. (October 2007)

    Fellow of the Royal Society - 1954
    Commander of the Order of the British Empire - 1963
    Order of the Companions of Honour - 1981
    Order of Merit (Commonwealth) - 1986
    Nobel Prize in Chemistry - 1958, 1980
     

    (来源: 桑格研究院 )


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