Susumu Tonegawa

Susumu Tonegawa (利根川 進, Tonegawa Susumu, born September 5, 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.

Susumu Tonegawa
Tonegawa early in his tenure at MIT
Born (1939-09-05) September 5, 1939
Nagoya, Japan
NationalityJapan
Alma mater
Known forAntibody diversity
E-box
V(D)J recombination
Awards
Scientific career
FieldsGenetics, Immunology, Neuroscience
Institutions
Academic advisors
InfluencedAdrian Hayday (postdoc),[1]

Alcino Silva (postdoc), Kenneth Poss (graduate student),

Peter Mombaert (graduate student)
Websitetonegawalab.mit.edu/susumu-tonegawa

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 Institute 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 also served as Director of the RIKEN Brain Science Institute from 2009 to 2017.

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's lab pioneered introductory transgenic and gene-knockout technologies in mammalian systems. He was involved in early work demonstrating the importance of CaMKII- (1992) and the NMDA receptor-dependent synaptic plasticity (1996) 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 demonstrated 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] social memory, 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, Hidde Tonegawa, Hanna Tonegawa, and Satto Tonegawa (deceased).

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

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, Joe Z.; Huerta, Patricio T.; Tonegawa, Susumu (1996). "The Essential Role of Hippocampal CA1 NMDA Receptor–Dependent Synaptic Plasticity in Spatial Memory". Cell. 87 (7): 1327–1338. doi:10.1016/S0092-8674(00)81827-9. PMID 8980238. S2CID 2730362.
  • 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

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. PMID 3917858. S2CID 34582929.
  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. "The Nobel Prize in Physiology or Medicine 1987".
  6. "Researchers reverse Fragile X Syndrome symptoms in adult mice".
  7. Liu, X.; et al. (2012). "Optogenetic stimulation of a hippocampal engram activates fear memory recall". Nature. 484 (7394): 381–385. Bibcode:2012Natur.484..381L. doi:10.1038/nature11028. PMC 3331914. PMID 22441246.
  8. Redondo, Roger L.; Kim, Joshua; Arons, Autumn L.; Ramirez, Steve; Liu, Xu; Tonegawa, Susumu (2014). "Bidirectional switch of the valence associated with a hippocampal contextual memory engram". Nature. 513 (7518): 426–430. Bibcode:2014Natur.513..426R. doi:10.1038/nature13725. PMC 4169316. PMID 25162525.
  9. Ramirez, Steve; Liu, Xu; MacDonald, Christopher J.; Moffa, Anthony; Zhou, Joanne; Redondo, Roger L.; Tonegawa, Susumu (2015). "Activating positive memory engrams suppresses depression-like behaviour". Nature. 522 (7556): 335–339. Bibcode:2015Natur.522..335R. doi:10.1038/nature14514. PMC 5583720. PMID 26085274.
  10. Ryan, T. J.; Roy, D. S.; Pignatelli, M.; Arons, A.; Tonegawa, S. (2015). "Engram cells retain memory under retrograde amnesia". Science. 348 (6238): 1007–1013. Bibcode:2015Sci...348.1007R. doi:10.1126/science.aaa5542. PMC 5583719. PMID 26023136.
  11. Recipients of American Academy of Arts and Sciences Fellow award | MIT Biology Archived 2016-03-26 at the Wayback Machine
  12. Recipients of National Academy of Sciences Member award | MIT Biology Archived 2017-01-07 at the Wayback Machine
  13. Shampo, MA; Kyle, RA; Steensma, DP (2011). "Susumu Tonegawa--Japan's first Nobel laureate in physiology or medicine". Mayo Clin Proc. 86 (2): e14. doi:10.4065/mcp.2010.0818. PMC 3031445. PMID 21282480.
  14. 利根川 進様 京都大学名誉博士授与式典 式辞 （2004年4月12日） — 京都大学
  15. Honorary Doctor of Science Professor Susumu TONEGAWA
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