Laboratory for Cell Function Dynamics

"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.

Research Subjects

• Development of a new microscopy system
• Development of fluorescent indicators for various cellular events using novel fluorescent protein
• Local and physiological Ca2+ imaging

Publications

1. Miyawaki A.:
   "Red fluorescent proteins: chromophore formation and cellular applications. "
   Curr. Opin. Struct. Biol., 22 (5): 679-688. (2012).
2. Miyawaki A.:
   "Proteins on the move: insights gained from fluorescent protein technologies."
   Nat. Rev. Mol. Cell Biol.,12 (10): 656-668 (2011).
3. Mori R, Ikematsu K, Kitaguchi T, Kim SE, Okamoto M, Chiba T, Miyawaki A, Shimokawa I, and Tsuboi T.:
   "Release of TNF-α from macrophages is mediated by small GTPase Rab37"
   Eur J Immunol (2011)
4. Katayama H, Kogure T, Mizushima N, Yoshimori T, Miyawaki A.:
   "Dimerization of MT1-MMP during cellular invasion detected by flourescence resonance energy transfer"
   Biochem J (2011)
5. Katayama H, Kogure T, Mizushima N, Yoshimori T, and Miyawaki A.:
   "A sensitive and quantitative technique for detecting autophagic events based on lysosomal delivery"
   Chem Biol, 18(8), 1042-52 (2011)
6. Hama H, Kurokawa H, Kawano H, Ando R, Shimogori T, Noda H, Fukami K, Sakaue-Sawano A, and Miyawaki A.:
   "Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain"
   Nat Neurosci (2011)
7. Jovic A, Wade SM, Miyawaki A, Neubig RR, Linderman JJ, and Takayama S.:
   "Hi-Fi transmission of periodic signals amid cell-to-cell variability"
   Mol Biosyst, 7(7), 2238-44 (2011)
8. Harada T, Matsuishi K, Oishi Y, Isobe K, Suda A, Kawan H, Mizuno H, Miyawaki A, Midorikawa K, and Kannari F.:
   "Temporal control of local plasmon distribution on Au nanocrosses by ultra-broadband femtosecond laser pulses and its application for selective two-photon excitation of multiple fluorophores"
   Opt Express, 19(14), 13618-27 (2011)
9. Nakajima Y, Kuranaga E, Sugimura K, Miyawaki A, and Miura M.:
   "Nonautonomous apoptosis is triggered by local cell cycle progression during epithelial replacement in Drosophila"
   Mol Cell Biol, 31(12), 2499-512 (2011)
10. Miyawaki A.:
    "Development of probes for cellular functions using fluorescent proteins and fluorescence resonance energy transfer"
    Annu Rev Biochem, 80, 357-73 (2011)