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[핫이슈] 2012년 노벨 생리의학상
[핫이슈] 2012년 노벨 생리의학상 저자 BRIC (생물학연구정보센터)
등록일 2012.10.09
조회 9567  인쇄하기 주소복사 트위터 공유 페이스북 공유 
키워드: 핫이슈, 노벨생리의학상

The Nobel Prize in Physiology or Medicine 2012
 


The Nobel Prize in Physiology or Medicine 2012 was awarded jointly to Sir John B. Gurdon and Shinya Yamanaka "for the discovery that mature cells can be reprogrammed to become pluripotent"

기획 및 구성 : 김수정


올해 노벨 생리의학상 수상자로 야마나카 신야 일본 교토대 재생의학연구소 교수(50)와 존 거든 영국 케임브리지대 거든연구소장(79) 2명이 선정됐다. 야마나카 교수는 유도만능줄기세포(iPS)의 세계적 권위자로, 거든은 핵 이식 및 복제 분야 개척자로 알려져 있다. 스웨덴 카롤린스카연구소 노벨위원회는 8일 야마나카와 거든의 두 연구가 합쳐져서 엄청난 진보를 이뤄냈고, 또 새로운 발견을 위한 계기가 되었고, 질병을 연구 진단하고 치료할 새로운 기회를 제공했다고 선정 이유를 밝혔다.

관련뉴스
- 노벨 생리의학상, 英 존 거든 경ㆍ日 야마나카 신야 수상(THE SCIENCE) 2012-10-08
- 노벨 생리의학상 수상자 日 야마나카 교수..임상의 지망하다 좌절 끝 연구자 전환(e헬스통신) 2012-10-08
- 노벨의학상 英 거던 "놀랍고 감사한 일"” (e헬스통신) 2012-10-08
- 노벨의학상 안겨준 ‘역분화줄기세포’ 수상 의미는?(이투데이) 2012-10-08
- Reprogrammed Cells Earn Nobel Honor (ScienceNow) 2012-10-08
- Nobel Prize in Physiology or Medicine 2012 Awarded for Discovery That Mature Cells Can Be Reprogrammed to Become Pluripotent d (ScienceDaily) 2012-10-08

About the Nobel prize Laureate






Press Release

The Nobel Assembly at Karolinska Institutet has today decided to award
The Nobel Prize in Physiology or Medicine 2012
jointly to
John B. Gurdon and Shinya Yamanaka
for the discovery that mature cells can be reprogrammed
to become pluripotent


 Summary

The Nobel Prize recognizes two scientists who discovered that mature, specialised cells can be reprogrammed to become immature cells capable of developing into all tissues of the body. Their findings have revolutionised our understanding of how cells and organisms develop.

John B. Gurdon discovered in 1962 that the specialisation of cells is reversible. In a classic experiment, he replaced the immature cell nucleus in an egg cell of a frog with the nucleus from a mature intestinal cell. This modified egg cell developed into a normal tadpole. The DNA of the mature cell still had all the information needed to develop all cells in the frog.

Shinya Yamanaka discovered more than 40 years later, in 2006, how intact mature cells in mice could be reprogrammed to become immature stem cells. Surprisingly, by introducing only a few genes, he could reprogram mature cells to become pluripotent stem cells, i.e. immature cells that are able to develop into all types of cells in the body.

These groundbreaking discoveries have completely changed our view of the development and cellular specialisation. We now understand that the mature cell does not have to be confined forever to its specialised state. Textbooks have been rewritten and new research fields have been established. By reprogramming human cells, scientists have created new opportunities to study diseases and develop methods for diagnosis and therapy.

Life - a journey towards increasing specialisation All of us developed from fertilized egg cells. During the first days after conception, the embryo consists of immature cells, each of which is capable of developing into all the cell types that form the adult organism. Such cells are called pluripotent stem cells. With further development of the embryo, these cells give rise to nerve cells, muscle cells, liver cells and all other cell types - each of them specialised to carry out a specific task in the adult body. This journey from immature to specialised cell was previously considered to be unidirectional. It was thought that the cell changes in such a way during maturation that it would no longer be possible for it to return to an immature, pluripotent stage.

Frogs jump backwards in development
John B. Gurdon challenged the dogma that the specialised cell is irreversibly committed to its fate. He hypothesised that its genome might still contain all the information needed to drive its development into all the different cell types of an organism. In 1962, he tested this hypothesis by replacing the cell nucleus of a frog's egg cell with a nucleus from a mature, specialised cell derived from the intestine of a tadpole. The egg developed into a fully functional, cloned tadpole and subsequent repeats of the experiment yielded adult frogs. The nucleus of the mature cell had not lost its capacity to drive development to a fully functional organism.

Gurdon's landmark discovery was initially met with scepticism but became accepted when it had been confirmed by other scientists. It initiated intense research and the technique was further developed, leading eventually to the cloning of mammals. Gurdon's research taught us that the nucleus of a mature, specialized cell can be returned to an immature, pluripotent state. But his experiment involved the removal of cell nuclei with pipettes followed by their introduction into other cells. Would it ever be possible to turn an intact cell back into a pluripotent stem cell?

A roundtrip journey - mature cells return to a stem cell state
Shinya Yamanaka was able to answer this question in a scientific breakthrough more than 40 years after Gurdon´s discovery. His research concerned embryonal stem cells, i.e. pluripotent stem cells that are isolated from the embryo and cultured in the laboratory. Such stem cells were initially isolated from mice by Martin Evans (Nobel Prize 2007) and Yamanaka tried to find the genes that kept them immature. When several of these genes had been identified, he tested whether any of them could reprogram mature cells to become pluripotent stem cells.

Yamanaka and his co-workers introduced these genes, in different combinations, into mature cells from connective tissue, fibroblasts, and examined the results under the microscope. They finally found a combination that worked, and the recipe was surprisingly simple. By introducing four genes together, they could reprogram their fibroblasts into immature stem cells!

The resulting induced pluripotent stem cells (iPS cells) could develop into mature cell types such as fibroblasts, nerve cells and gut cells. The discovery that intact, mature cells could be reprogrammed into pluripotent stem cells was published in 2006 and was immediately considered a major breakthrough.

From surprising discovery to medical use
The discoveries of Gurdon and Yamanaka have shown that specialised cells can turn back the developmental clock under certain circumstances. Although their genome undergoes modifications during development, these modifications are not irreversible. We have obtained a new view of the development of cells and organisms.

Research during recent years has shown that iPS cells can give rise to all the different cell types of the body. These discoveries have also provided new tools for scientists around the world and led to remarkable progress in many areas of medicine. iPS cells can also be prepared from human cells.

For instance, skin cells can be obtained from patients with various diseases, reprogrammed, and examined in the laboratory to determine how they differ from cells of healthy individuals. Such cells constitute invaluable tools for understanding disease mechanisms and so provide new opportunities to develop medical therapies.

Sir John B. Gurdon was born in 1933 in Dippenhall, UK. He received his Doctorate from the University of Oxford in 1960 and was a postdoctoral fellow at California Institute of Technology. He joined Cambridge University, UK, in 1972 and has served as Professor of Cell Biology and Master of Magdalene College. Gurdon is currently at the Gurdon Institute in Cambridge.

Shinya Yamanaka was born in Osaka, Japan in 1962. He obtained his MD in 1987 at Kobe University and trained as an orthopaedic surgeon before switching to basic research. Yamanaka received his PhD at Osaka City University in 1993, after which he worked at the Gladstone Institute in San Francisco and Nara Institute of Science and Technology in Japan. Yamanaka is currently Professor at Kyoto University and also affiliated with the Gladstone Institute.

Key publications:
Gurdon, J.B. (1962). The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. Journal of Embryology and Experimental Morphology 10:622-640.

Takahashi, K., Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663-676.


사진 및 내용 출처: http://nobelprize.org/ 


Shinya Yamanaka

Curriculum Vitae
1981-1987 Kobe University, School of Medicine, Kobe, Japan
1989-1993 Osaka City University Graduate School, Osaka, Japan Division of Medicine
1987-1989 Resident, National Osaka Hospital, Osaka, Japan
1993-1995 Postdoctoral Fellow Gladstone Institute of Cardiovascular Disease, San Francisco, USA
1995-1996 Staff Research Investigator, Gladstone Institute of Cardiovascular Disease
1996-1999 Assistant Professor, Osaka City University, Medical School, Osaka, Japan
1999-2003 Associate Professor, Nara Institute of Science and Technology, Nara, Japan
2003-2005 Professor, Nara Institute of Science and Technology
2004-2010 Professor Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
2007- Senior Investigator, Gladstone Institute of Cardiovascular Disease The J. David Gladstone Institutes, San Francisco, CA USA
2007-2012 Professor, Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University Kyoto, Japan
2008-2010 Director, Center for iPS cell Research and Application (CiRA), iCeMS Kyoto University, Kyoto, Japan
2010- Director, Center for iPS cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
2012- Professor, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
2012-2013 President, Internatinoal Society for Stem Cell Research (ISSCR)

Publications

출처: http://www.cira.kyoto-u.ac.jp/e/research/yamanaka_master.html
 
Sir John B. Gurdon

Career

Gosney res fell Caltech 1962; Univ of Oxford: department demonstrator Dept of Zoology 1963-64, res fell ChCh 1962-72, lectr Dept of Zoology 1965-72; visiting res fell Carnegie Inst Baltimore 1965, head Cell Biology Div MRC Laboratory of Molecular Biology Cambridge 1979-83, Fullerian prof of physiology and comparative anatomy Royal Inst 1985-91, John Humphrey Plummer prof of cell biology and chm Wellcome/CRC Inst Cambridge 1991-2001, master Magdalene Coll Cambridge 1995-2002; fell: Churchill Coll Cambridge 1973-94, Eton Coll 1978-93; chm Co of Biologists Cambridge 2001-; govr Wellcome Tst 1995-2000; hon foreign memb: American Acad of Arts and Sciences, US Nat Acad of Sciences, Belgian Acad of Letters and Fine Arts 1984, Lombardy Acad of Sci Italy 1989, Academie des Sciences France 1990; foreign memb: American Philosophical Soc 1983, Inst of Med USA 2003; Liveryman Worshipful Co of Goldsmiths; hon fell: ChCh Oxford, Magdalene Coll Cambridge 2002, Churchill Coll Cambridge 2007; Hon DSc: Univ of Chicago 1978, Univ of Paris 1982, Univ of Oxford 1985, Univ of Hull 1998, Univ of Glasgow 2000, Univ of Cambridge 2007, Vrije Universiteit Brussel 2009, Andres Bello Univ Chile 2012; FRS 1971; Awards Albert Brachet Prize Belgian Royal Acad 1968, Scientific Medal Zoological Soc 1968, Feldberg Fndn Award 1975, Paul Ehrlich Award (Germany) 1977, Comfort Crookshank Award for Cancer Res 1983, William Bate Hardy Prize Cambridge Philosophical Soc 1984, Prix de Charles Leopold Mayer Acad des Scis France 1984, Ross Harrison Prize 1985, CIBA Medal Biochemical Soc 1985, Royal Medal Royal Soc 1985, Emperor Hirohito International Prize (Japan) 1987, Wolf Prize in Medicine (Israel) 1989, Jan Waldenstrom Medal 1991, Distinguished Serv Award (Miami) 1992, Jean Brachet Memorial Prize 2000, Conklin Medal 2001, Copley Medal Royal Soc 2003, Rosenstiel Basic Science Award (USA) 2009, Albert Lasker Award for Basic Medical Research 2009, Nobel Prize for medicine or physiology 2012


Research interests:

The differentiated state of adult cells is remarkably stable, and ensures the normal function of our body tissues and organs. Hardly ever does a cell of one kind change into a different kind of cell. However, there are certain experimental procedures by which gene expression of a specialised adult cell can be reversed to that of an embryonic cell. This opens the way to provide therapeutically useful replacement cells of any kind from other readily available cells of another kind, such as skin.

One procedure for reversing the differentiated state of a cell is by transplanting its nucleus to an egg or oocyte. Our aim is to understand how eggs or oocytes achieve this, so as to identify the reprogramming molecules involved, and thus, eventually, to improve the efficiency of this route towards cell replacement without immunosuppression.

We use the growing eggs (“oocytes”) of amphibia to activate embryo-expressing genes in the transplanted nuclei of adult mammalian cells. We have recently identified polymerised actin and its cofactors as a significant component of this oocyte transcriptional apparatus for reprogramming somatic nuclei. A question of at least as much importance is how the differentiated state of a cell makes its nucleus resistant to the reprogramming activities of an oocyte. Genes that become transcriptionally repressed in normal development are of this kind. Such genes show an epigenetic memory of their quiescent state. We have identified macroH2A as one chromatin protein that helps to confer an inactive state of genes on the inactive X chromosome of female mammals. We have recently developed a procedure by which chromosomal proteins can be progressively removed from somatic cell nuclei to improve embryonic gene reactivation. This can lead to the identification of chromosomal components that resist reprogramming by oocytes. The removal of these could greatly improve the efficiency of nuclear reprogramming.


Selected publications
Miyamoto K, Pasque V, Jullien J and Gurdon JB (2011) Nuclear actin polymerization is required for transcriptional reprogramming of Oct4 by oocytes. Genes & Development 25(9):946-958

Pasque V, Gillich A, Garrett N and Gurdon JB (2011) Histone variant macroH2A confers resistance to nuclear reprogramming. EMBO J 6;30(12):2373-87

Jullien J, Halley-Stott RP, Miyamoto K, Pasque V and Gurdon JB (2011) Mechanisms of nuclear reprogramming by eggs and oocytes: a deterministic process? Nature Reviews Molecular & Cell Biology, 12, 453-459

Narbonne P, Simpson DE and Gurdon JB (2011) Deficient induction response in a Xenopus nucleocytoplasmic hybrid. PLoS Biology 9(11):e101197

Pasque V, Jullien J, Miyamoto K, Halley-Stott RP and Gurdon JB (2011) Genetic and epigenetic factors affecting nuclear reprogramming efficiency. Trends in Genetics 27(12)516-525

출처: http://www.brighthub.com/science/genetics/articles/21417.aspx
http://www.debretts.com/people/biographies/browse/g/2055/John+Bertrand.aspx
 

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