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Laboratory for Comprehensive Bioimaging

Tomonobu Watanabe


Team Leader

Tomonobu Watanabe (Ph.D.)

Watanabe of Riken

Original HP

Cells can be thought of as complex systems in a dynamic equilibrium between multiple states that fluctuate stochastically. Our aim is to construct a numerical model that describes the common mechanisms regulating high-order function in complex biological systems. To understand the behavior of these systems, it is necessary to observe state transitions while at the same time quantitatively describing their dynamics. We are developing novel imaging systems that combine three major techniques to achieve this aim: 1) imaging systems which measure protein position, dynamics and the surrounding environment , 2) novel cell culture systems which can control and perturb the chemical/mechanical environment, and 3) custom designed biochemical/inorganic sensors that can visualize the status of the cell. The developed techniques will provide significant insight on the regulation of tissues, immunity, metabolism and aging by understanding the fundamental mechanisms that give rise to these disparate and complex systems.In turn, the information gained will significantly improve our ability to diagnose and treat diseases and advance the design of new medicines.

Research Topics

  • Development of linear and non-linear bio-optical measurement technologies
  • Development of high-throughput microscopy
  • iPS cell research by using the above technologies
  • Deep, non-invasive in vivo imaging by novel NIR optics
  • Development of novel fluorescent protein probes

Selected Publications

  • Germond, A., Kumar, V., Ichimura, T., Moreau, J., Furusawa, C., Fujita, H., et al.
    "Raman spectroscopy as a tool for ecology and evolution"
    Journal of the Royal Society Interface 14, 20170174 (2017) doi:10.1098/rsif.2017.0174
  • Ichimura, T., Chiu, L., Fujita, K., Machiyama, H., Yamaguchi, T., Watanabe, T. M., et al.
    "Non-label immune cell state prediction using Raman spectroscopy"
    Sci. Rep. 6, 37562 (2016) doi:10.1038/srep37562
  • Germond, A., Fujita, H., Ichimura, T. & Watanabe, T.M.
    "Design and development of genetically encoded fluorescent sensors to monitor intracellular chemical and physical parameters"
    Biophys. Rev. 8, 121-138 (2016) doi:10.1007/s12551-016-0195-9
  • Morikawa, T. J., Fujita, H., Kitamura, A., Horio, T., Yamamoto, J., Kinjo, M., et al.
    "Dependence of fluorescent protein brightness on protein concentration in solution and enhancement of it"
    Sci. Rep. 6, 22342 (2016) doi:10.1038/srep22342
  • Kaneshiro, J., Watanabe, T. M., Fujita, H. & Ichimura, T.
    "Full control of polarization state with a pair of electro-optic modulators for polarization-resolved optical microscopy"
    Appl. Opt. 55, 1082-1089 (2016) doi:10.1364/ao.55.001082
  • Ichimura, T., Chiu, L., Fujita, K., Machiyama, H., Kawata, S., Watanabe, T. M., et al.
    "Visualizing the appearance and disappearance of the attractor of differentiation using Raman spectral imaging"
    Sci. Rep. 5, 11358 (2015) doi:10.1038/srep11358
  • Fujita, H., Esaki, T., Masujima, T., Hotta, A., Kim, S. H., Noji, H., et al.
    "Comprehensive chemical secretory measurement of single cells trapped in a micro-droplet array with mass spectrometry"
    RSC Adv. 5, 16968-16971 (2015) doi:10.1039/c4ra12021c
  • Higuchi, S., Watanabe, T. M., Kawauchi, K., Ichimura, T. & Fujita, H.
    "Culturing of mouse and human cells on soft substrates promote the expression of stem cell markers"
    J. Biosci. Bioeng. 117, 749-755 (2014) doi:10.1016/j.jbiosc.2013.11.011
  • Ichimura, T., Chiu, L., Fujita, K., Kawata, S., Watanabe, T. M., Yanagida, T., et al.
    "Visualizing Cell State Transition Using Raman Spectroscopy"
    PLoS One 9, e84478 (2014) doi:10.1371/journal.pone.0084478
  • Watanabe, T. M., Fujii, F., Jin, T., Umemoto, E., Miyasaka, M., Fujita, H., et al.
    "Four-Dimensional Spatial Nanometry of Single Particles in Living Cells Using Polarized Quantum Rods"
    Biophys. J. 105, 555-564 (2013) doi:10.1016/j.bpj.2013.07.001