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Chief Scientist Laboratories Cellular Informatics Laboratory

Chief Scientist: Yasushi Sako (D.Sc.)

Research Summary

Yasushi  Sako(D.Sc.)

Complex and flexible behaviors of living cells are outputs of intracellular signaling molecule systems. Unitary reactions in molecular systems are stochastic events, use energy as low as thermal fluctuation, and the average number of molecules involved is sometimes less than 100 suggesting significant number fluctuation in individual cells. Thus, molecular systems are suffering large fluctuations even though cells look like to be acting purposively searching both internal and external environments. Cells seem to have special mechanisms to suppress fluctuations but it is also possible that cells have evolved to use fluctuations positively. How fluctuating molecular systems determine complex and flexible cellular behaviors? We are developing single-molecule analysis technologies in living cells and trying to find the answer "goes down with" everyone.

Main Research Fields

  • Biology

Related Research Fields

  • Complex Systems
  • Biological Sciences
  • Biophysics


  • Intracellular Signal Transduction
  • Bioimaging

Selected Publications

Papers with an asterisk(*) are based on research conducted outside of RIKEN.

  • 1. Okamoto, K., Hibino, K., and Sako, Y.:
    "In-cell single-molecule FRET measurements reveal three conformational state changes in RAF protein"
    Biochim. Biophys. Acta. Gen. Subj. 1864(2), 129358 (2020).
  • 2. Yanagawa, M., Hiroshima, M., Togashi, Y., Abe, M., Yamashita, T., Shichida, Y., Murata, M., Ueda, M., and Sako, Y.:
    "Single-molecule diffusion-based estimation of ligand effects on G protein-coupled receptors"
    Sci. Signal. 11(548), eaao1917 (2018).
  • 3. Hiroshima, M., Pack, C.-G., Kaizu, K., Takahashi, K., Ueda, M., and Sako, Y.:
    "Transient acceleration of epidermal growth factor receptor dynamics produces higher-order signaling clusters"
    J. Mol. Biol. 430(9), 1386-1401 (2018).
  • 4. Maeda, R., Sato, T., Okamoto, K., Yanagawa, M., and Sako, Y.:
    "Lipid-protein interplay in dimerization of juxtamembrane domains of epidermal growth factor receptor"
    Biophys. J. 114(4), 893-903 (2018).
  • 5. Nakamura, Y., Umeki, N., Abe, M., and Sako, Y.:
    "Mutation-specific mechanisms of hyperactivation of Noonan syndrome SOS molecules detected with single-molecule imaging in living cells"
    Sci. Rep. 7(1), 14153 (2017).
  • 6. Arata, Y., Hiroshima, M., Pack, C.-G., Ramanujam, R., Motegi, F., Nakazato, K., Wiseman, P. W., Sawa, H., Kobayashi, T. J., Brandão, H. B., Shibata, T., and Sako, Y.:
    "Cortical polarity of the RING protein PAR-2 is maintained by exchange rate kinetics at the cortical-cytoplasm boundary"
    Cell Rep. 16(8), 2156-2168 (2016).
  • 7. Takanezawa, S., Morita, S.-i., Ozaki, Y., and Sako, Y.:
    "Raman spectral dynamics of single cells in the early stages of growth factor stimulation"
    Biophys. J. 108(9), 2148-2157 (2015).
  • 8. Mouri, K., and Sako, Y.:
    "Optimality conditions for cell-fate heterogeneity that maximize the effects of growth factors in PC12 cells"
    PLoS Comp. Biol. 9(11), e1003320 (2013).
  • 9. Hiroshima, M., Saeki, Y., Okada-Hatakeyama, M., and Sako, Y.:
    "Dynamically varying interactions between heregulin and ErbB proteins detected by single-molecule analysis in living cells"
    Proc. Natl. Acad. Sci. USA. 109(35), 13984-13989 (2012).
  • 10. Okamoto, K., and Sako, Y.:
    "Variational Bayes analysis of a photon-based hidden Markov model for single-molecule FRET trajectories"
    Biophys. J. 103(6), 1315-1324 (2012).

Recent Research Results

Annual research report

Related Links

Lab Members

Principal investigator

Yasushi Sako
Chief Scientist

Core members

Junichi Aikawa
Senior Research Scientist
Mitsuhiro Abe
Senior Research Scientist
Yukinobu Arata
Senior Research Scientist
Kenji Okamoto
Senior Research Scientist
Toshihiro Nagamine
Senior Research Scientist
Akihiro Yamamoto
Senior Technical Scientist
Nobuhisa Umeki
Research Scientist
Michio Hirosnima
Research Scientist
Ryo Maeda
Research Scientist
Masataka Yanagawa
Research Scientist
Ryo Yoshizawa
Student Trainee
Yutaro Kuwashima
Student Trainee
Hiromi Sato
Technical Staff II
Mutsumi Nakanishi
Technical Staff II
Toshihide Kobayashi
Senior Visiting Scientist
Yoshio Hirabayashi
Senior Visiting Scientist
Changi Back
Visiting Scientist
Peter Jurica
Visiting Scientist
Toshiko Sawai

Contact Information

2-1 Hirosawa, Wako, Saitama 351-0198, Japan
Email: sako-lab [at] riken.jp