RIKEN Center for Brain Science Laboratory for Cell Function Dynamics

Laboratory Head: Atsushi Miyawaki (M.D., Ph.D.)

Japanese Page

Research Summary

"Why bio-imaging, i.e. real time fluorescence imaging?" Currently, this is a topic of great interest in the bioscience community. Many molecules involved in signal transduction have been identified, and the hierarchy among those molecules has also been elucidated. It is not uncommon to see a signal transduction diagram in which arrows are used to link molecules to show enzyme reactions and intermolecular interactions. To obtain a further understanding of a signal transduction system, however, the diagram must contain the three axes in space as well as a fourth dimension, time, because all events are controlled ingeniously in space and time. Since the isolation of green fluorescent protein (GFP) from the bioluminescent jellyfish in 1992 and later with its relatives, researchers have been awaiting the development of a tool, which enables the direct visualization of biological functions. This has been increasingly enhanced by the marriage of GFP with fluorescence resonance energy transfer (FRET) or fluorescence cross-correlation spectroscopy (FCCS), and is further expanded upon by the need for "post-genomic analyses." It is not my intent to discourage the trend seeking the visualization of biological function. I would like to propose that it is time to evaluate the true asset of "bio-imaging" for its potential and limitations in order to utilize and truly benefit from this novel technique.

Keywords

Bioimaging
Fluorescent protein
chromophore

Selected Publications

1.Watanabe T, Seki T, Fukano T, Sakaue-Sawano A, Karasawa S, Kubota M, Kurokawa H, Inoue K, Akatsuka J, Miyawaki A.:
"Genetic visualization of protein interactions harnessing liquid phase transitions."
Sci. Rep., 7: 46380. doi: 10.1038/srep46380 (2017).
2.Miyawaki A.:
"Exploiting the cyanobacterial light-harvesting machinery for developing fluorescent probes."
Nat. Methods, 13 (9): 729-730 (2016).
3.Hama H, Hioki H, Namiki K, Hoshida T, Kurokawa H, Ishidate F, Kaneko T, Akagi T, Saito T, Saido T, Miyawaki A.:
"Deep Imaging of Cleared Brain by Confocal Laser-Scanning Microscopy."
Protocol Exchange, doi:10.1038/protex.2016.019 (2016).
4.Hama H, Hioki H, Namiki K, Hoshida T, Kurokawa H, Ishidate F, Kaneko T, Akagi T, Saito T, Saido T, Miyawaki A.:
"ScaleS: an optical clearing palette for biological imaging."
Nat. Neurosci., 18 (10): 1518-1529 (2015).
5.Miyawaki A, Jaffrey SR.:
"Editorial overview: Molecular imaging: Cellular imaging approaches."
Curr. Opin. Chem. Biol., 27: v-vi (2015).
6.Miyawaki A, Niino Y.:
"Molecular spies for bioimaging - Fluorescent protein-based probes."
Mol. Cell, 48 (4): 632–643 (2015).
7.Tsutsui H, Jinno Y, Shoda K,Tomita A, Matsuda M,Yamashita E, Katayama H, Nakagawa A, Miyawaki A.:
"A Diffraction-Quality Protein Crystal Processed as an Autophagic Cargo."
Mol. Cell, 58 (1), 186-193 (2015).
8.Sakaue-Sawano A, Hoshida T, Yo M, Takahashi R, Ohtawa K, Arai T, Takahashi E, Noda S, Miyoshi H, Miyawaki A.:
"Visualizing developmentally programmed endoreplication in mammals using ubiquitin oscillators."
Development, 140 (22), 4624-4632 (2013).
9.Kumagai A, Ando R, Miyatake H, Greimel P, Kobayashi T, Hirabayashi Y, Shimogori T, Miyawaki A.:
"A Bilirubin-Inducible Fluorescent Protein from Eel Muscle."
Cell, 153 (7): 1602-1611 (2013).
10.Shimozono S, Iimura T, Kitaguchi T, Higashijima SI, Miyawaki A.:
"Visualization of an endogenous retinoic acid gradient across embryonic development."
Nature, 496 (7445): 363-366 (2013).