Susumu Tonegawa

is a Japanese scientist who was the sole recipient of the Nobel Prize for Physiology or Medicine in 1987 for his discovery of V(D)J recombination, the genetic mechanism which produces antibody diversity. 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. 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. This process is known as V(D)J recombination.

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, 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.

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.

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, social memory, as well as their role in brain disorders such as depression, amnesia, 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

1982 – Louisa Gross Horwitz Prize
1983 – Gairdner Foundation International Award
1984 – 45px|ribbon barOrder of Culture (Bunkakunsho), Emperor of Japan
1984 – Foreign Associate, American Academy of Arts and Sciences of the United States
1986 – Foreign Associate, National Academy of Sciences of the United States
1986 – Robert Koch Prize
1987 – Albert Lasker Award for Basic Medical Research
1987 – Nobel Prize for Physiology or Medicine
1995 – honored on a stamp (Scott No. 1635c) issued by Gambia
2004 – Honorary Degree, Kyoto University
2006 – Member, American Association for the Advancement of Science
2007 – RIKEN Fellow
2009 – Honorary Degree, City University of Hong Kong
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.
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.

References

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
www.tonegawalab.org
Susumu Tonegawa on The Picower Institute