Susumu Tonegawa

Susumu Tonegawa
Susumu Tonegawa, 2013
Born	September 6, 1939 Nagoya, Japan
Nationality	Japan
Fields	Genetics, Immunology, Neuroscience
Institutions	Massachusetts Institute of Technology RIKEN Brain Science Institute Howard Hughes Medical Institute
Alma mater	Kyoto University University of California, San Diego
Academic advisors	Masaki Hayashi Renato Dulbecco
Known for	Antibody diversity
Influenced	Adrian Hayday (postdoc)[1]
Notable awards	Louisa Gross Horwitz Prize (1982) Order of Culture (1984) Nobel Prize for Physiology or Medicine (1987)
Website tonegawalab.mit.edu/susumu-tonegawa

Susumu Tonegawa (利根川 進 Tonegawa Susumu, born September 6, 1939) is a Japanese scientist who was the sole recipient of the Nobel Prize for Physiology or Medicine in 1987, for his discovery of the genetic mechanism that produces antibody diversity.^[2] Although he won the Nobel Prize for his work in immunology, Tonegawa is a molecular biologist by training and he again changed fields following his Nobel Prize win; he now studies neuroscience, examining the molecular, cellular and neuronal basis of memory formation and retrieval.

Early Life and Education

Tonegawa was born in Nagoya, Japan and attended Hibiya High School in Tokyo.^[3] While a student at Kyoto University, Tonegawa became fascinated with operon theory after reading papers by François Jacob and Jacques Monod, whom he credits in part for inspiring his interest in molecular biology.^[4] Tonegawa graduated from Kyoto University in 1963 and, due to limited options for molecular biology study in Japan at the time, moved to the University of California, San Diego to do his doctorate study under Dr. Masaki Hayashi. He received his Ph.D. in 1968.

Career

Tonegawa conducted post-doctoral work at the Salk Institute in San Diego in the laboratory of Renato Dulbecco. With encouragement from Dr. Dulbecco, Tonegawa moved to the Basel Institute for Immunology in Basel, Switzerland in 1971, where he transitioned from molecular biology into immunology studies and carried out his landmark immunology studies.

In 1981, Tonegawa became a professor at the Massachusetts Institute of Technology. In 1994, he was appointed as the first Director of the MIT Center for Learning and Memory, which developed under his guidance into The Picower Center for Learning and Memory. Tonegawa resigned his directorship in 2006 and currently serves as a Picower Professor of Neuroscience and Biology and a Howard Hughes Medical Institute Investigator.

Tonegawa has also served as Director of the RIKEN Brain Science Institute since 2009.

Research

Discovery of Immunity Diversity

Tonegawa’s Nobel Prize work elucidated the genetic mechanism of the adaptive immune system, which had been the central question of immunology for over 100 years. Prior to Tonegawa’s discovery, one early idea to explain the adaptive immune system suggested that each gene produces one protein; however, there are under 19,000 genes in the human body which nonetheless can produce millions of antibodies. In experiments beginning in 1976, Tonegawa showed that genetic material rearranges itself to form millions of antibodies. Comparing the DNA of B cells (a type of white blood cell) in embryonic and adult mice, he observed that genes in the mature B cells of the adult mice are moved around, recombined, and deleted to form the diversity of the variable region of antibodies.^[5] In 1983, Tonegawa also discovered a transcriptional enhancer element associated with antibody gene complex, the first cellular enhancer element.

Neuroscience

Shortly following his Nobel Prize in 1990, Tonegawa again changed fields from immunology to neuroscience, where he has focused his research in the ensuing years.

Tonegawa early in his tenure at MIT.

Tonegawa’s lab pioneered introductory transgenic and gene-knockout technologies in mammalian systems. He discovered an enzyme called CaMKII (1992) as well as a synaptic protein NMDA receptor (1996), which plays crucial roles in memory formation.

Tonegawa’s lab discovered that dendritic neuronal spines in the temporal cortex are a likely target for treatment of Fragile X Syndrome. With one dosage of the inhibitor drug FRAX586, Tonegawa showed a marked reduction of FXS symptoms in the mouse model.^[6]

Tonegawa was an early adopter of optogenetics and biotechnology in neuroscience research, leading to his groundbreaking work identifying and manipulating memory engram cells. In 2012, his lab demonstrated that the activation of a specific sub-population of mouse hippocampal neurons, labelled during a fear conditioning paradigm, is sufficient to evoke a behavioral response correlated with a precise memory trace. This confirmed for the first time that memory information is stored in specific cellular ensembles in the hippocampus, now frequently called memory engram cells.^[7]

More recently, his lab continues to employ optogenetic technology and virus injection techniques to expand their findings on the engram cell ensemble. Notably, Tonegawa has uncovered the role of memory engram cell ensembles in memory valence,^[8] as well as their role in brain disorders such as depression,^[9] amnesia,^[10] and Alzheimer’s disease. These works provide proofs of concept for future medical treatments in humans through the manipulation of memory engram ensembles.

Personal life

Tonegawa currently resides in the Boston area with his wife, Mayumi Yoshinari Tonegawa, who worked as an NHK (Japan Broadcasting Corporation) director/interviewer and is now a freelance science writer. The Tonegawas have three children.

Tonegawa is a fan of the Boston Red Sox, and threw out an opening pitch during their 2004 World Series championship season.

Selected awards and honors

1982 Louisa Gross Horwitz Prize of Columbia University
1983 Gairdner Foundation International Award of the Gairdner Foundation, Toronto, Canada
1984 Order of Culture (Bunkakunsho), Emperor of Japan
1986 Foreign Associate, National Academy of Sciences of the United States
1986 Robert Koch Prize of the Robert Koch Foundation, Bonn, West Germany
1987 Albert and Mary Lasker Award (Basic Research), New York City
1987 Nobel Prize for Physiology or Medicine, Stockholm, Sweden
2007 RIKEN Fellow, Saitama, Japan
2010 David M. Bonner Lifetime Achievement Award, UCSD

Selected publications

• List of publications by Susumu Tonegawa
• Tonegawa, S. (1983). Somatic generation of antibody diversity. Nature, 302(5909), 575-581.
• Gillies, S. D., Morrison, S. L., Oi, V. T., & Tonegawa, S. (1983). A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell, 33(3), 717-728.
• Mombaerts, P., Iacomini, J., Johnson, R. S., Herrup, K., Tonegawa, S., & Papaioannou, V. E. (1992). RAG-1-deficient mice have no mature B and T lymphocytes. Cell, 68(5), 869-877.
• Silva, A. J., Stevens, C. F., Tonegawa, S., & Wang, Y. (1992). Deficient hippocampal long-term potentiation in alpha-calcium-calmodulin kinase II mutant mice. Science, 257(5067), 201-206.
• Haas, W., Pereira, P., & Tonegawa, S. (1993). Gamma/delta cells. Annual review of immunology, 11(1), 637-685.
• Tsien, J. Z., Huerta, P. T., & Tonegawa, S. (1996). The essential role of hippocampal CA1 NMDA receptor–dependent synaptic plasticity in spatial memory. Cell, 87(7), 1327-1338.
• Poss, K. D., & Tonegawa, S. (1997). Reduced stress defense in heme oxygenase 1-deficient cells. Proceedings of the National Academy of Sciences, 94(20), 10925-10930.
• Shen, J., Bronson, R. T., Chen, D. F., Xia, W., Selkoe, D. J., & Tonegawa, S. (1997). Skeletal and CNS defects in Presenilin-1-deficient mice. Cell, 89(4), 629-639.
• Nakazawa, K., Quirk, M. C., Chitwood, R. A., Watanabe, M., Yeckel, M. F., Sun, L. D., Kato, A., Carr, C.A., Johnston, D., Wilson, M.A., & Tonegawa, S. (2002). Requirement for hippocampal CA3 NMDA receptors in associative memory recall. Science, 297(5579), 211-218.
• Liu, X., Ramirez, S., Pang, P. T., Puryear, C. B., Govindarajan, A., Deisseroth, K., & Tonegawa, S. (2012). Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature, 484(7394), 381-385.
• Ramirez, S., Liu, X., Lin, P. A., Suh, J., Pignatelli, M., Redondo, R. L., Ryan, T.J., & Tonegawa, S. (2013). Creating a false memory in the hippocampus. Science, 341(6144), 387-391.

See also

• List of Japanese Nobel laureates
• List of Nobel laureates affiliated with Kyoto University

References

1. Hayday, A (1985). "Structure, organization, and somatic rearrangement of T cell gamma genes". Cell 40 (2): 259–269. doi:10.1016/0092-8674(85)90140-0.
2. "The MIT 150: 150 Ideas, Inventions, and Innovators that Helped Shape Our World". The Boston Globe. May 15, 2011. Retrieved August 8, 2011.
3. Autobiography on Nobel official website
4. Autobiography on Nobel official website
5. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1987/press.html
6. http://news.mit.edu/2013/researchers-reverse-autism-symptoms-0319
7. Liu, X.; et al. (2012). "Optogenetic stimulation of a hippocampal engram activates fear memory recall". Nature 484: 381–385. doi:10.1038/nature11028. PMID 22441246.
8. http://www.nature.com/nature/journal/v513/n7518/full/nature13725.html
9. http://www.nature.com/nature/journal/v522/n7556/full/nature14514.html
10. http://science.sciencemag.org/content/348/6238/1007

External links

• Faculty Webpage at MIT Biology
• Description of research at the Picower Institute for Learning and Memory
• The Official Site of Louisa Gross Horwitz Prize
• http://picower.mit.edu/Faculty/Principal%20Investigators/susumu-tonegawa Susumu Tonegawa] on The Picower Institute