Title of Presentation

“Cruising inside cells”

The behavior of biochemical molecules moving around in cells makes me think of a school of whales wandering in the ocean, captured by the Argus system on the artificial satellite. When bringing a whale back into the sea — with a transmitter on its dorsal fin, every staff member hopes that it will return safely to a school of its species. A transmitter is now minute in size, but it was not this way before. There used to be some concern that a whale fitted with a transmitter could be given the cold shoulder and thus ostracized by other whales for “wearing something annoying.” How is whale’s wandering related to the tide or a shoal of small fish? What kind of interaction is there among different species of whales? We Human Beings have attempted to fully understand this fellow creature in the sea both during and since the age of whale fishing.

In a live cell imaging experiment, a luminescent probe replaces a transmitter. We label a luminescent probe on a specific region of a biological molecule and bring it back into a cell. We can then visualize how the biological molecule behaves in response to external stimulation. Since luminescence is a physical phenomenon, we can extract various kinds of information by making full use of its characteristics.

Cruising inside cells in a supermicro corps, gliding down in a microtubule like a roller coaster, pushing our ways through a jungle of chromatin while hoisting a flag of nuclear localization signal — we are reminded to retain a playful and adventurous perspective at all times. What matters is mobilizing all capabilities of science and giving full play to our imagination. We believe that serendipitous findings can arise out of such a sportive mind, a frame of mind that prevails when enjoying whale-watching.

Over the past two decades, various genetically encoded probes have been generated principally using fluorescent proteins. I will discuss how the probes have advanced our understanding of the spatio-temporal regulation of biological functions, such as cell-cycle progression, autophagy, and metabolism, inside cells, neurons, embryos, and brains. I will also speculate on how these approaches will continue to improve due to the various features of fluorescent proteins.

Profile

A brief Biography

Mar. 1987	M.D., Keio University School of Medicine
Mar. 1991	Ph.D., Osaka University Graduate School of Medicine (Molecular Neurobiology) Research field: The molecular basis of the calcium channel activity of IP3 receptors
Apr. 1991	Research Fellow, Japan Society for the Promotion of Science Research field: Structure-function relationships of IP3 receptors
Apr. 1993 – Dec. 1998	Assistant Professor, Institute of Medical Science, The　University of Tokyo Research field: IP3/calcium dynamics
Oct. 1995	HFSP long-term fellowship, University of California San Diego, Dept. of Pharmacology Research field: Development of a calcium probe
Oct. 1997	Research Pharmacologist, University of California San Diego, Dept. of Pharmacology Research field: Development of a calcium probe
Jan. 1999 –	Laboratory Head, Laboratory for Cell Function Dynamics, Advanced Technology Development Group, RIKEN Brain Science Institute Research field: Fluorescent bioimaging
Jan. 2004 – Mar. 2009	Group Director, Advanced Technology Development Group, RIKEN Brain Science Institute Research field: Fluorescent bioimaging
Jul. 2005 – Mar. 2010	Visiting Professor, Department of Proteomics, Research Center for Bioinformatics, Institute of Molecular and Cellular Biosciences, The University of Tokyo
Apr. 2006 – Mar. 2011	Visiting Professor, Laboratory of Developmental Dynamics, National Institute for Basic Biology, The National Institute of Natural Sciences
Oct. 2006 – Mar. 2012	Research Director, ERATO Life Function Dynamics Project, Japan Science and Technology Agency
Apr.2007 –	Visiting Professor, Department of Molecular Neurobiology, Graduate School of Advanced Science and Engineering, Waseda University
Apr. 2008 –	Deputy Director, RIKEN Brain Science Institute
Apr. 2009 –	Visiting Professor, Keio University School of Medicine
Apr. 2010 – Mar. 2011	Visiting Professor, Faculty of Science, Toho University
Apr. 2012 –	Visiting Professor, Graduate School of Nanobioscience, Yokohama City University
Apr. 2013 –	Laboratory Head, Biotechnological Optics Research Team, RIKEN Center for Advanced Photonics

Details of selected Awards and Honors

Oct. 2004	Yamazaki-Teiichi Prize, Foundation for Promotion of Material Science and Technology of Japan (Biological Science & Technology)
Dec. 2006	JSPS (Japan Society for the Promotion of Science) Prize (Biological Sciences)
Mar. 2007	Tsukahara Memorial Award
Jun. 2007	Kitasato Award, Keio University School of Medicine Alumni Association
Apr. 2008	Prize for Science and Technology (Development Category), The Commendation for Science and Technology by the Minister of Education, Culture, Sports, Science and Technology,
Feb. 2012	Inoue Prize for Science
Jun. 2013	Fujihara Award
Dec. 2014	Arthur Kornberg Memorial Award
Oct. 2015	W. Alden Spencer Award (Columbia University)
Feb. 2016	Shimadzu Award

A list of selected Publications

Hama H, Hioki H, Namiki K, Hoshida T, Kurokawa H, Ishidate F, Kaneko T, Akagi T, Saito T, Saido T, Miyawaki A. (2015) ScaleS: an optical clearing palette for biological imaging. Nature Neuroscience, 18: 1518-1529.

Kumagai A, Ando R, Miyatake H, Greimel P, Kobayashi T, Hirabayashi Y, Shimogori T, Miyawaki A. (2013) A Bilirubin-Inducible Fluorescent Protein from Eel Muscle. Cell, 153: 1602-1611.

Shimozono S, Iimura T, Kitaguchi T, Higashijima SI, Miyawaki A. (2013) Visualization of an endogenous retinoic acid gradient across embryonic development. Nature, 496: 363-366.

Hama H, Kurokawa H, Kawano H, Ando R, Shimogori T, Noda H, Fukami K, Sakaue-Sawano A, Miyawaki A. (2011) Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain. Nature Neuroscience, 14: 1481-1488.

Sakaue-Sawano A, Kurokawa H, Morimura T, Hanyu A, Hama H, Osawa H, Kashiwagi S, Fukami K, Miyata T, Miyoshi H, Imamura T, Ogawa M, Masai H, Miyawaki A. (2008) Visualizing Spatiotemporal Dynamics of Multicellular Cell Cycle Progression. Cell, 132: 487-498.

Ando R, Mizuno H, Miyawaki A. (2004) Regulated fast nucleocytoplasmic shuttling observed by reversible protein highlighting. Science, 306: 1370-1373.

Mizuno H, Mal TK, Tong KI, Ando R, Furuta T, Ikura M, Miyawaki A. (2003) Photo-induced peptide cleavage in the green-to-red conversion of a fluorescent protein. Mol. Cell, 12: 1051-1058.

Ando R, Hama H, Yamamoto-Hino M, Mizuno H, Miyawaki A. (2002) An optical marker based on the UV-induced green-to-red photoconversion of a fluorescent protein. Proc. Natl. Acad. Sci. USA., 99: 12651-12656.

Nagai T, Ibata K, Park ES, Kubota M, Mikoshiba K, Miyawaki A. (2002) A variant of yellow fluorescent protein with fast and efficient maturation for cell-biological applications. Nature Biotechnology, 20: 87-90.

Miyawaki A, Llopis J, Heim R, McCaffery JM, Adams JA, Ikura M, Tsien RY. (1997) Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin. Nature, 388: 882-887.