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Live imaging of cell-to-cell communication

Planned Research

Project AreaResonance Biology for Innovative Bioimaging
Project/Area Number 15H05949
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyoto University

Principal Investigator

MATSUDA MICHIYUKI  京都大学, 生命科学研究科, 教授 (10199812)

Co-Investigator(Kenkyū-buntansha) 隅山 健太  国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (00370114)
平島 剛志  京都大学, 医学研究科, 講師 (10620198)
築地 真也  名古屋工業大学, 工学(系)研究科(研究院), 教授 (40359659)
平塚 拓也  京都大学, 医学研究科, 特定講師 (90641639)
Project Period (FY) 2015-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥194,090,000 (Direct Cost: ¥149,300,000、Indirect Cost: ¥44,790,000)
Fiscal Year 2019: ¥37,050,000 (Direct Cost: ¥28,500,000、Indirect Cost: ¥8,550,000)
Fiscal Year 2018: ¥37,180,000 (Direct Cost: ¥28,600,000、Indirect Cost: ¥8,580,000)
Fiscal Year 2017: ¥37,180,000 (Direct Cost: ¥28,600,000、Indirect Cost: ¥8,580,000)
Fiscal Year 2016: ¥37,180,000 (Direct Cost: ¥28,600,000、Indirect Cost: ¥8,580,000)
Fiscal Year 2015: ¥45,500,000 (Direct Cost: ¥35,000,000、Indirect Cost: ¥10,500,000)
Keywords蛍光イメージング / 蛍光顕微鏡 / バイオセンサー / 上皮細胞増殖因子 / FRET / PKA / ERK / 蛍光タンパク質 / 筋再生 / イメージング / 細胞生物学 / 再生 / 蛍光バイオセンサー / BRET / 生体イメージング / 発光イメージング / FRETバイオセンサー / 分子プローブ / 蛍光共鳴エネルギー移動 / タンパク質リン酸化酵素 / FRETバイオセンサー
Outline of Final Research Achievements

We have developed many FRET biosensors for protein kinases including ERK, PKA, ROCK, Tak1, AMPK, and so on. Furthermore, we developed transgenic mice expressing these FRET biosensors and observed many organs including skin, lung, platelet, muscle, bladder, and small intestine to visualize cell-to-cell communication. For example, we have shown for the first time that ERK activity in the skin and small intestine fluctuates and that such ERK activation can be propagated to the neighboring cells.

Academic Significance and Societal Importance of the Research Achievements

細胞を構成する多様な分子の活性変化が細胞の機能をそしてひいては個体の機能を制御していることはよく知られている。しかし、技術的な困難性のために、実際に生きた組織で分子活性を顕微鏡レベルの解像度で観察することは極めて難しい。本研究では分子活性を多光子顕微鏡下に観察することで、これまで知られていなかった細胞間コミュニケーションの実態を明らかにする技術基盤を確立した。この技術は、例えば薬剤がどうして効くのかといった健康に直結する問題等に関して、試験管内の知見と個体の反応との大きなギャップを埋める非常に有用な手段を提供する。

Report

(6 results)
  • 2020 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report

Research Products

(41 results)

All 2020 2019 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (23 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 23 results,  Open Access: 9 results) Presentation (15 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results) Remarks (2 results)

  • [Int'l Joint Research] University of Helsinki(フィンランド)

    • Country Name
      FINLAND
    • Counterpart Institution
      University of Helsinki
    • Related Report
      2018 Annual Research Report
  • [Journal Article] Biliverdin Reductase-A Deficiency Brighten and Sensitize Biliverdin-binding Chromoproteins2020

    • Author(s)
      Kobachi Kenju、Kuno Sota、Sato Shinya、Sumiyama Kenta、Matsuda Michiyuki、Terai Kenta
    • Journal Title

      Cell Structure and Function

      Volume: 45 Pages: 131~141

    • DOI

      10.1247/csf.20010

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Altered G1 signaling order and commitment point in cells proliferating without CDK4/6 activity2020

    • Author(s)
      Liu Chad、Konagaya Yumi、Chung Mingyu、Daigh Leighton H.、Fan Yilin、Yang Hee Won、Terai Kenta、Matsuda Michiyuki、Meyer Tobias
    • Journal Title

      Nature Communications

      Volume: 11 Pages: 5305

    • DOI

      10.1038/s41467-020-18966-9

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rhodopsin-mediated light-off-induced protein kinase A activation in mouse rod photoreceptor cells2020

    • Author(s)
      Sato Shinya、Yamashita Takahiro、Matsuda Michiyuki
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 117 Pages: 26996~27003

    • DOI

      10.1073/pnas.2009164117

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intravital imaging reveals cell cycle-dependent myogenic cell migration during muscle regeneration2020

    • Author(s)
      Konagaya Yumi、Takakura Kanako、Sogabe Maina、Bisaria Anjali、Liu Chad、Meyer Tobias、Sehara-Fujisawa Atsuko、Matsuda Michiyuki、Terai Kenta
    • Journal Title

      Cell Cycle

      Volume: 19 Pages: 3167~3181

    • DOI

      10.1080/15384101.2020.1838779

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Single-Cell Activation of the cAMP-Signaling Pathway in 3D Tissues with FRET-Assisted Two-Photon Activation of bPAC2020

    • Author(s)
      Kinjo Tomoaki、Watabe Tetsuya、Kobachi Kenju、Terai Kenta、Matsuda Michiyuki
    • Journal Title

      ACS Chemical Biology

      Volume: 15 Pages: 2848~2853

    • DOI

      10.1021/acschembio.0c00333

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Booster, a Red-Shifted Genetically Encoded F?rster Resonance Energy Transfer (FRET) Biosensor Compatible with Cyan Fluorescent Protein/Yellow Fluorescent Protein-Based FRET Biosensors and Blue Light-Responsive Optogenetic Tools2020

    • Author(s)
      Watabe Tetsuya、Terai Kenta、Sumiyama Kenta、Matsuda Michiyuki
    • Journal Title

      ACS Sensors

      Volume: 5 Pages: 719~730

    • DOI

      10.1021/acssensors.9b01941

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Indispensable role of STIL in the regulation of cancer cell motility through the lamellipodial accumulation of ARHGEF7?PAK1 complex2019

    • Author(s)
      Ito Hideaki、Tsunoda Takumi、Riku Miho、Inaguma Shingo、Inoko Akihito、Murakami Hideki、Ikeda Hiroshi、Matsuda Michiyuki、Kasai Kenji
    • Journal Title

      Oncogene

      Volume: 39 Pages: 1931~1943

    • DOI

      10.1038/s41388-019-1115-9

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Two Decades of Genetically Encoded Biosensors Based on F?rster Resonance Energy Transfer2019

    • Author(s)
      Terai Kenta、Imanishi Ayako、Li Chunjie、Matsuda Michiyuki
    • Journal Title

      Cell Structure and Function

      Volume: 44 Pages: 153~169

    • DOI

      10.1247/csf.18035

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Live-Cell FRET Imaging Reveals a Role of Extracellular Signal-Regulated Kinase Activity Dynamics in Thymocyte Motility2018

    • Author(s)
      Konishi Yoshinobu、Terai Kenta、Furuta Yasuhide、Kiyonari Hiroshi、Abe Takaya、Ueda Yoshihiro、Kinashi Tatsuo、Hamazaki Yoko、Takaori-Kondo Akifumi、Matsuda Michiyuki
    • Journal Title

      iScience

      Volume: 10 Pages: 98~113

    • DOI

      10.1016/j.isci.2018.11.025

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gliding Basal Cell Migration of the Urothelium during Wound Healing2018

    • Author(s)
      Sano Takeshi、Kobayashi Takashi、Ogawa Osamu、Matsuda Michiyuki
    • Journal Title

      The American Journal of Pathology

      Volume: 188 Pages: 2564~2573

    • DOI

      10.1016/j.ajpath.2018.07.010

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Novel Morphological Marker for the Analysis of Molecular Activities at the Single-cell Level2018

    • Author(s)
      Imanishi Ayako、Murata Tomokazu、Sato Masaya、Hotta Kazuhiro、Imayoshi Itaru、Matsuda Michiyuki、Terai Kenta
    • Journal Title

      Cell Structure and Function

      Volume: 43 Pages: 129~140

    • DOI

      10.1247/csf.18013

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dynamic MAPK/ERK Activity Sustains Nephron Progenitors through Niche Regulation and Primes Precursors for Differentiation2018

    • Author(s)
      Ihermann-Hella Anneliis、Hirashima Tsuyoshi、Kupari Jussi、Kurtzeborn Kristen、Li Hao、Kwon Hyuk Nam、Cebrian Cristina、Soofi Abdul、Dapkunas Arvydas、Miinalainen Ilkka、Dressler Gregory R.、Matsuda Michiyuki、Kuure Satu
    • Journal Title

      Stem Cell Reports

      Volume: 11 Pages: 912~928

    • DOI

      10.1016/j.stemcr.2018.08.012

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A platform of BRET-FRET hybrid biosensors for optogenetics, chemical screening, and in vivo imaging2018

    • Author(s)
      Komatsu Naoki、Terai Kenta、Imanishi Ayako、Kamioka Yuji、Sumiyama Kenta、Jin Takashi、Okada Yasushi、Nagai Takeharu、Matsuda Michiyuki
    • Journal Title

      Scientific Reports

      Volume: 8 Pages: 8984

    • DOI

      10.1038/s41598-018-27174-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Composite regulation of ERK activity dynamics underlying tumour-specific traits in the intestine2018

    • Author(s)
      Muta Yu、Fujita Yoshihisa、Sumiyama Kenta、Sakurai Atsuro、Taketo M. Mark、Chiba Tsutomu、Seno Hiroshi、Aoki Kazuhiro、Matsuda Michiyuki、Imajo Masamichi
    • Journal Title

      Nature Communications

      Volume: 9 Pages: 2174

    • DOI

      10.1038/s41467-018-04527-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Dynamic ERK signaling regulation in intestinal tumorigenesis2018

    • Author(s)
      Muta Yu、Matsuda Michiyuki、Imajo Masamichi
    • Journal Title

      Molecular & Cellular Oncology

      Volume: 5 Pages: 1506684

    • DOI

      10.1080/23723556.2018.1506684

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] In Vivo FRET Imaging of Tumor Endothelial Cells Highlights a Role of Low PKA Activity in Vascular Hyperpermeability2016

    • Author(s)
      Yamauchi Fumio、Kamioka Yuji、Yano Tetsuya、Matsuda Michiyuki
    • Journal Title

      Cancer Res

      Volume: 76 Pages: 5266~5276

    • DOI

      10.1158/0008-5472.can-15-3534

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intravital imaging of mouse urothelium reveals activation of extracellular signal-regulated kinase by stretch-induced intravesical release of ATP2016

    • Author(s)
      Sano Takeshi、Kobayashi Takashi、Negoro Hiromitsu、Sengiku Atsushi、Hiratsuka Takuya、Kamioka Yuji、Liou Louis S.、Ogawa Osamu、Matsuda Michiyuki
    • Journal Title

      Physiol Rep

      Volume: 4 Pages: e13033~e13033

    • DOI

      10.14814/phy2.13033

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of Aging-Associated Gene Expression Signatures That Precede Intestinal Tumorigenesis2016

    • Author(s)
      Okuchi Yoshihisa、Imajo Masamichi、Mizuno Rei、Kamioka Yuji、Miyoshi Hiroyuki、Taketo Makoto Mark、Nagayama Satoshi、Sakai Yoshiharu、Matsuda Michiyuki
    • Journal Title

      Plos One

      Volume: 11 Pages: e0162300

    • DOI

      10.1371/journal.pone.0162300

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell Density-Dependent Increase in Tyrosine-Monophosphorylated ERK2 in MDCK Cells Expressing Active Ras or Raf2016

    • Author(s)
      Kawabata Noriyuki、Matsuda Michiyuki
    • Journal Title

      Plos One

      Volume: 11 Pages: e0167940

    • DOI

      10.1371/journal.pone.0167940

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cancer‐specific mutations in p53 induce the translation of Δ160p53 promoting tumorigenesis2016

    • Author(s)
      Candeias Marco M、Hagiwara Masatoshi、Matsuda Michiyuki
    • Journal Title

      EMBO Rep

      Volume: 17 Pages: 1542~1551

    • DOI

      10.15252/embr.201541956

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intercellular propagation of extracellular signal-regulated kinase activation revealed by in vivo imaging of mouse skin.2015

    • Author(s)
      Hiratsuka T, Fujita Y, Naoki H, Aoki K, Kamioka Y, Matsuda M.
    • Journal Title

      eLife

      Volume: 4 Pages: e05178

    • DOI

      10.7554/eLife.05178

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intravital imaging reveals gow BRAF inhibition generates drugtolerant microenvironments with high integrin beta1/FAK signaling2015

    • Author(s)
      Hirata E, Girotti MR, Viros A, Hooper S, Spencer-Dene B, Matsuda M,
    • Journal Title

      Cancer Cell

      Volume: 27 Pages: 574-88

    • DOI

      10.1016/j.ccell.2015.03.008

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Heterogeneity in ERK activity as visualized by in vivo FRET imaging of mammary tumor cells developed in MMTV-Neu mice2015

    • Author(s)
      Kumagai Y, Naoki H, Nakasyo E, Kamioka Y, Kiyokawa E, Matsuda M.
    • Journal Title

      Oncogene

      Volume: 34 Pages: 1051-7

    • DOI

      10.1038/onc.2014.28

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Live-cell FRET imaging reveals a role of ERK activity dynamics in thymocyte motility2018

    • Author(s)
      Yoshinobu Konishi, Kenta Terai, Takaya Abe, Yoko Hamazaki, Akifumi Takaori-Kondo and Michiyuki Matsud
    • Organizer
      The 60th American Society of Hematology Annual Meeting and Exhibition
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Timelapse FRET imaging reveals the correlation between the strength of ERK activation in NK cells and the fate of conjugated target cells.2018

    • Author(s)
      Hiroshi Ichise, Kenta Terai, Michiyuki Matsuda
    • Organizer
      The 17th Meeting of Society for natural immunity
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of four dimensional histology for live imaging2017

    • Author(s)
      Ayako Imanishi; Masaya Sato; Kenta Terai; Kenta Sumiyama; Kazuhiro Hotta; Michiyuki Matsuda
    • Organizer
      The 1st ABiS Symposium
    • Related Report
      2016 Annual Research Report
  • [Presentation] 高感度のAMPK FRETバイオセンサーを用いた生体内AMPK活性の不均一性2017

    • Author(s)
      Yumi Konagaya; Kenta Terai; Michiyuki Matsuda
    • Organizer
      第4回発生における代謝を考える会
    • Related Report
      2016 Annual Research Report
  • [Presentation] A highly sensitive FRET biosensor for AMP-activated protein kinase (AMPK) reveals heterogeneous cellular responses in vitro and in vivo.2017

    • Author(s)
      Yumi Konagaya; Kenta Terai; Michiyuki Matsuda
    • Organizer
      第1回ABiSシンポジウム
    • Related Report
      2016 Annual Research Report
  • [Presentation] Age-related DNA methylation and altered gene expression precede loss of heterozygosity of the Apc gene in ApcΔ716 mice.2016

    • Author(s)
      Yoshihisa Okuchi
    • Organizer
      Tenth AACR-JCA Joint Conference on Breakthrough in Cancer Research: From Biology to Therapeutics
    • Place of Presentation
      Hyatt Regency Maui(Maui, U.S.A)
    • Year and Date
      2016-02-17 – 2016-02-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In vivo FRET imaging of tumor endothelial cells highlights a role of low PKA activity in vascular hyperpermeability2016

    • Author(s)
      Michiyuki Matsuda
    • Organizer
      Lorne Cancer Conference
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] FRETマウスの多光子顕微鏡観察2016

    • Author(s)
      松田道行
    • Organizer
      第68回日本細胞生物学会
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 組織細胞間コミュニケーションのライブイメージングに資する細胞形態マーカー発現マウスの作成2016

    • Author(s)
      今西彩子、小松直貴、隅山健太、松田道行
    • Organizer
      第68回日本細胞生物学会大会
    • Related Report
      2016 Annual Research Report
  • [Presentation] Two-photon-excited fluorescence excitation spectra of red fluorophores and fluorescent proteins.2016

    • Author(s)
      Yoshinobu Konishi; Yuji Kamioka and Michiyuki Matsuda
    • Organizer
      第68回日本細胞生物学会
    • Related Report
      2016 Annual Research Report
  • [Presentation] Visualization of AMPK activity by fluorescence resonance energy transfer-based biosensor in vivo.2016

    • Author(s)
      Yumi Konagaya; Yusuke Hirao; Masamichi Imajo; Yuji Kamioka; Michiyuki Matsuda
    • Organizer
      日本細胞生物学会
    • Related Report
      2016 Annual Research Report
  • [Presentation] マウス小腸オルガノイドにおけるシグナル伝達経路の解析2016

    • Author(s)
      牟田優; 今城正道; 松田道行
    • Organizer
      第68回日本細胞生物学会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 新規オルガノイド培養法を用いた肝芽腫発生機構の解析2016

    • Author(s)
      今城正道、松田道行
    • Organizer
      第68回細胞生物学会大会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 二光子顕微鏡による腸管腫瘍発生の可視化は正常腸管細胞の不均一性を明らかにする2015

    • Author(s)
      奥知慶久
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08 – 2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 変異型ras、raf 導入細胞の細胞密集による抑制2015

    • Author(s)
      河鰭憲幸
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08 – 2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Remarks] 新着論文概要

    • URL

      http://www.fret.lif.kyoto-u.ac.jp/project.htm#summary

    • Related Report
      2019 Annual Research Report
  • [Remarks] 研究概要

    • URL

      http://www.fret.lif.kyoto-u.ac.jp/project.htm

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report

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Published: 2015-07-02   Modified: 2022-11-04  

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