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Imaging of molecular functions in cells with nanometer accuracy and constructing models to explain them

Planned Research

Project AreaMolecular Science for Nanomedicine
Project/Area Number 23107002
Research Category

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

Allocation TypeSingle-year Grants
Review Section Science and Engineering
Research InstitutionThe University of Tokyo

Principal Investigator

Higuchi Hideo  東京大学, 大学院理学系研究科(理学部), 教授 (90165093)

Co-Investigator(Kenkyū-buntansha) 茅 元司  東京大学, 理学(系)研究科(研究院), 助教 (00422098)
Project Period (FY) 2011-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥89,700,000 (Direct Cost: ¥69,000,000、Indirect Cost: ¥20,700,000)
Fiscal Year 2015: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
Fiscal Year 2014: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2013: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2012: ¥25,090,000 (Direct Cost: ¥19,300,000、Indirect Cost: ¥5,790,000)
Fiscal Year 2011: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000)
Keywords1分子 / 1粒子 / 細胞 / 運動 / マウス / in vivo / がん細胞 / イメージング / 筋肉 / 幹細胞 / 非侵襲 / 好中球 / GFP / ナノメートル
Outline of Final Research Achievements

We took in vivo and in vitro images of single molecules and particles in mice and culture cells to understand the function of molecules. In vivo imaging, we images neutrophil labeled with quantum dots and cancer cells expressing tubulin-GFP in mouse auricles by spinning confocal microscope. The individual cancer cells, neutrophils and vesicles transporting in the neutrophil in mice were clear observed even at high spatiotemporal resolution of ~10ms and ~10nm. The speed of vesicle transport was much higher than that in purified cells.
To understand the damage of cancer cells quantitatively for cancer therapy, we took the phase contrast images of cancer cells and analyzed the intensity fluctuation (standard deviation of intensity) of each pixels in images. The magnitude of the fluctuation decreased with progress of cell damages. Long term observation of the fluctuation is available to detect the cell damage.

Report

(6 results)
  • 2016 Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (56 results)

All 2017 2016 2015 2014 2013 2012 2011

All Journal Article (15 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 11 results,  Acknowledgement Compliant: 4 results) Presentation (36 results) (of which Int'l Joint Research: 10 results,  Invited: 10 results) Book (4 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Quantitative evaluation of malignant gliomas damage induced by photoactivation of IR700 dye2016

    • Author(s)
      Morito Sakuma, Sayaka Kita and Hideo Higuchi
    • Journal Title

      Science and Technology of Advanced Materials

      Volume: 17 Issue: 1 Pages: 473-482

    • DOI

      10.1080/14686996.2016.1205936

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Analysis of spontaneous oscillations for a three state power stroke model2016

    • Author(s)
      Takumi Washio, Seine A. Shintani, Hideo Higuchi and Toshiaki Hisada
    • Journal Title

      Physical Review E

      Volume: 22 Issue: 2 Pages: 473-482

    • DOI

      10.1103/physreve.95.022411

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] In vivo muscle force and muscle power during near-maximal frog jumps2016

    • Author(s)
      Eug Kuan Moo, Daniel R Peterson, Timothy R Leonard, Motoshi Kaya, Walter Herzog
    • Journal Title

      PLoS One

      Volume: 12 Issue: 3 Pages: 1-12

    • DOI

      10.1371/journal.pone.0173415

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Predictive diagnosis of the risk of breast cancer recurrence after surgery by single-particle quantum dot imaging.2015

    • Author(s)
      Gonda K, Miyashita M, Higuchi H, Tada H, Watanabe TM, Watanabe M, Ishida T, Ohuchi N.
    • Journal Title

      Scientific Report.

      Volume: 22(5) Issue: 1 Pages: 14322-14322

    • DOI

      10.1038/srep14322

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dynein arms are strain-dependent direction-switching force generators.2015

    • Author(s)
      Shingyoji, C., Nakano, I., Inoue, Y. and Higuchi, H.
    • Journal Title

      Cytoskeleton

      Volume: 72 Issue: 8 Pages: 388-401

    • DOI

      10.1002/cm.21232

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 生物の普遍性2015

    • Author(s)
      樋口秀男
    • Journal Title

      生物物理学会誌

      Volume: 55 Pages: 285-285

    • NAID

      130005110033

    • Related Report
      2015 Annual Research Report
    • Open Access
  • [Journal Article] A novel approach for purification and selective capture of membrane vesicles of the periodontopathic bacterium, Porphyromonas gingivalis: membrane vesicles bind to magnetic beads coated with epoxy groups in a noncovalent, species-specific manner.2014

    • Author(s)
      Nakao R, Kikushima K, Higuchi H, Obana N, Nomura N, Bai D, Ohnishi M, Senpuku H.
    • Journal Title

      PLoS One.

      Volume: 9 Issue: 5 Pages: 1-10

    • DOI

      10.1371/journal.pone.0095137

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nano-scale measurement of biomolecules by optical microscopy and semiconductor nanoparticles2014

    • Author(s)
      Taro Ichimura, Takashi Jin, Hideaki Fujita, Hideo Higuchi, Tomonobu M. Watanabe
    • Journal Title

      Front. Physiol., fphys.

      Volume: 5 Pages: 1-13

    • DOI

      10.3389/fphys.2014.00273

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single quantum dot tracking reveals that an individual multivalent 2 HIV-1 Tat-protein transduction domain can activate machinery for 3 lateral transport and endocytosis2013

    • Author(s)
      3.Yasuhiro Suzuki*, Chandra Nath Roy, Warunya Promjunyaku, Hiroyasu Hatakeyama, Kohsuke Gonda, Junji Imamura, Biju Vasudevan Pillai, Noriaki Ohuchi, Makoto Kanzaki , Hideo Higuchi, and Mitsuo Kaku
    • Journal Title

      Mol. Cell Biol.

      Volume: 33 Issue: 15 Pages: 3039-3049

    • DOI

      10.1128/mcb.01717-12

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A non-invasive imaging for the in vivo tracking of high-speed vesicle transport in mouse neutrophils2013

    • Author(s)
      3.Kenji Kikushima, Sayaka Kita and Hideo Higuchi
    • Journal Title

      Scientific reports

      Volume: 3 Issue: 1 Pages: 1-10

    • DOI

      10.1038/srep01913

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Stiffness, working stroke and force of single myosins in skeletal muscle: Elucidation of these mechanical properties by non-linear elasticity2013

    • Author(s)
      Kaya. M. and H. Higuchi
    • Journal Title

      Cell and Mol. life Sci

      Volume: 70 Issue: 22 Pages: 4275-4292

    • DOI

      10.1007/s00018-013-1353-x

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of muscle forces using static optimization for different contractile conditions2013

    • Author(s)
      YUNUS ZIYA ARSLAN., AZIM JINHA., MOTOSHI KAYA., WALTER HERZOG
    • Journal Title

      Journal of Mechanics in Medicine and Biology

      Volume: 13 Issue: 03 Pages: 1-13

    • DOI

      10.1142/s021951941350022x

    • Related Report
      2012 Annual Research Report
  • [Journal Article] マウス個体内の1分子計測2011

    • Author(s)
      樋口秀男
    • Journal Title

      現代化学

      Volume: 488 Pages: 46-47

    • Related Report
      2011 Annual Research Report
  • [Journal Article] ナノバイオ2011

    • Author(s)
      樋口秀男
    • Journal Title

      理大科学フォーラム

      Volume: 8 Pages: 19-24

    • Related Report
      2011 Annual Research Report
  • [Journal Article] がん転移の生体ナノイメージング2011

    • Author(s)
      権田幸祐
    • Journal Title

      生物物理学

      Volume: 51 Pages: 82-83

    • Related Report
      2011 Annual Research Report
  • [Presentation] Quantitative evaluation of recovery from damage in cancer cells2017

    • Author(s)
      Morito Sakuma and Hideo Higuchi
    • Organizer
      Ito International Research Center
    • Place of Presentation
      東大(東京都文京区)
    • Year and Date
      2017-02-11
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Hideo Higuchi. Molecular Mechanism of Synchronous Force Generations among Myosin Molecules2017

    • Author(s)
      Motoshi Kaya, Takumi Washio, Hideo Higuchi
    • Organizer
      The 61st Annual Meeting of Biophysical Society
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2017-02-11
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The power stroke distance of human cytoplasmic dynein2017

    • Author(s)
      Yoshimi Kinoshita, Taketoshi Kambara, Kaori Nishikawa, Motoshi Kaya, Hideo Higuchi
    • Organizer
      The 61st Annual Meeting of Biophysical Society
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2017-02-11
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cooperative force generation by muscle myosin molecules interacting with actin filaments2016

    • Author(s)
      Hideo Higuchi
    • Organizer
      International Symposium on Universal Biology Univ. Tokyo
    • Place of Presentation
      東大(東京都文京区)
    • Year and Date
      2016-11-28
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Molecular mechanism of synchronous force generations among skeletal myosins. Symposium2016

    • Author(s)
      Motoshi Kaya
    • Organizer
      The 54th Annual Meeting of the Biophysical Society of Japan
    • Place of Presentation
      Intenational center, Tsukuba, Japan
    • Year and Date
      2016-09-25
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Cooperative force generation by muscle myosin molecules interacting with actin filaments2016

    • Author(s)
      Hideo Higuchi, Motoshi Kaya, Takumi Washio, Seine Shintani
    • Organizer
      KIAS Protein Science
    • Place of Presentation
      Soul, Korea
    • Year and Date
      2016-09-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanism of Synchronous Force Generations Between Skeletal Myosins in Myofilament2016

    • Author(s)
      Motoshi Kaya, Yoshiaki Tani, Takumi Washio, Toshiaki Hisada, Hideo Higuchi
    • Organizer
      The 19th European Bioenergetics Conference
    • Place of Presentation
      Riva del Garda, Italy
    • Year and Date
      2016-07-02
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ミオシン集団の持つ協同性と周期性2016

    • Author(s)
      樋口秀男, 茅元司, 鷲尾巧, 新谷正嶺
    • Organizer
      生物物理学会東北支部会
    • Place of Presentation
      東北大 (宮城県仙台市)
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Novel mouse xenograft model for noninvasive in vivo imaging of human tumor cell and tissue in the auricle.2015

    • Author(s)
      喜多清、樋口秀男
    • Organizer
      第120回日本解剖学会
    • Place of Presentation
      神戸国際会議場 (兵庫県 神戸市)
    • Year and Date
      2015-03-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] Intermolecular cooperativity of skeletal myosins enhances force output in myofilaments2015

    • Author(s)
      Motoshi Kaya, Yoshiaki Tani, Takumi Washi, Toshiaki Hisada and Hideo Higuchi
    • Organizer
      The 59th Annual Meeting of the Biophysical Society
    • Place of Presentation
      Convention Center(Baltimore、USA)
    • Year and Date
      2015-02-07
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Imaging of Porphyromonaus ginigivalis infection using quantum dot2014

    • Author(s)
      菊島健児、中尾龍馬、樋口秀男
    • Organizer
      日本免疫学会
    • Place of Presentation
      国立京都国際会館 (京都府 京都市)
    • Year and Date
      2014-12-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] Noninvasive in vivo imaging of neutrophil and tumor in mouse auricles2014

    • Author(s)
      Hideo Higuchi, Kenji Kikushima and Sayaka Kita
    • Organizer
      8th Internal Symposium on Nanomedicine
    • Place of Presentation
      愛媛大学(愛媛県 松山市)
    • Year and Date
      2014-12-06
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Novel mouse xenograft model for noninvasive in vivo imaging of human tumor cell and tissue in the auricle.2014

    • Author(s)
      Sayaka Kita and Hideo Higuchi
    • Organizer
      The American Society for Cell Biology
    • Place of Presentation
      Convention Center (Philadelphia, USA)
    • Year and Date
      2014-12-06
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 1分子計測技術を用いて効率的な筋収縮の仕組みを紐解く2014

    • Author(s)
      茅 元司
    • Organizer
      日本生化学会大会
    • Place of Presentation
      国立京都国際会館 (京都府京都市)
    • Year and Date
      2014-10-15
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 量子ドットを用いた脳がん幹細胞表面の膜たんぱく質の運動解析2014

    • Author(s)
      佐久間守仁、喜多清、樋口秀男
    • Organizer
      生物物理学会大会
    • Place of Presentation
      生物物理学会大会
    • Year and Date
      2014-09-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Trafficking of membrane protein PAR-1 carried by endocytotic vesicles in cancer cells2014

    • Author(s)
      Seohyun Lee、茅元司、樋 口秀男
    • Organizer
      生物物理学会大会
    • Place of Presentation
      コンベンションセンター(北海道 札幌市)
    • Year and Date
      2014-09-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] 蛍光量子ドットを用いた細胞内高速小胞輸送機構の解明2014

    • Author(s)
      菊島健児、樋口秀男
    • Organizer
      生物物理学会大会
    • Place of Presentation
      コンベンションセンター(北海道 札幌市)
    • Year and Date
      2014-09-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Noninvasive in vivo imaging of neutrophil and tumor in mouse auricles2014

    • Author(s)
      Hideo Higuchi, Kenji Kikushima and Sayaka Kita
    • Organizer
      A3 Foresight Symposium on Nanomedicine
    • Place of Presentation
      大観荘(宮城県 松島市)
    • Year and Date
      2014-09-02
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 蛍光量子ドットを用いた細胞内高速小胞輸送機構解明2014

    • Author(s)
      菊島健児、樋口秀男
    • Organizer
      ナノ学会大会
    • Place of Presentation
      おお ばくプラザ(京都府 宇治市)
    • Year and Date
      2014-05-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] Noninvasive in vivo imaging of neutrophil and tumor in mouse auricles2013

    • Author(s)
      Hideo Higuchi, Kenji Kikushima and Sayaka Kita
    • Organizer
      The International Symposium on Multi-Scale Muscle Mechanics
    • Place of Presentation
      北九州
    • Year and Date
      2013-11-07 – 2013-11-10
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Symposium on Biophysics toward In Vivo work2013

    • Author(s)
      Hideo Higuchi and Norio Fukuda
    • Organizer
      日本生物物理学会
    • Place of Presentation
      京都
    • Year and Date
      2013-10-28 – 2013-10-30
    • Related Report
      2013 Annual Research Report
  • [Presentation] Molecular properties and dynamics of single skeletal myosins designed for force generations in ensemble of myosin molecules2013

    • Author(s)
      茅元司、樋口秀男
    • Organizer
      日本生物物理学会年会
    • Place of Presentation
      京都
    • Year and Date
      2013-10-28 – 2013-10-30
    • Related Report
      2013 Annual Research Report
  • [Presentation] A non-invasive technique for the in vivo tracking of high-speed vesicle transport in mouse neutrophils2013

    • Author(s)
      菊島健児、喜多清、樋口秀男
    • Organizer
      日本生物物理学会年会
    • Place of Presentation
      京都
    • Year and Date
      2013-10-28 – 2013-10-30
    • Related Report
      2013 Annual Research Report
  • [Presentation] 量子ドットを用いたマウス耳内に おける白血球内小胞運動の非侵襲イメージング2013

    • Author(s)
      喜多清, 樋口秀男
    • Organizer
      ナノ学会
    • Place of Presentation
      東京
    • Year and Date
      2013-06-06 – 2013-06-08
    • Related Report
      2013 Annual Research Report
  • [Presentation] マウス内単一分子イメージング2013

    • Author(s)
      樋口秀男
    • Organizer
      国立感染症研究所学友会セミナー
    • Place of Presentation
      東京 国立感染症研究所
    • Year and Date
      2013-04-17
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Noninvasive in vivo imaging of Tumor cells in mouse Auricles.2013

    • Author(s)
      喜多清、菊島健児、樋口秀男
    • Organizer
      The 4th Taiwan-Japan Symposium on Nanomedicine
    • Place of Presentation
      Academia Sinca(Taipei)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Non-invasive in vivo imaging of vesicle movements of neutrophil in the mouse ear using quantum dots2012

    • Author(s)
      菊島健児、喜多清、樋口秀男
    • Organizer
      34th Naito conference
    • Place of Presentation
      シャトーレガトーキングダムサッポロ(北海道)
    • Related Report
      2012 Annual Research Report
  • [Presentation] A non-invasive method for the in vivo tracking of high-speed vesicle transport in mouse neutrophils2012

    • Author(s)
      菊島健児
    • Organizer
      6th International Symposium of Nanomedicine
    • Place of Presentation
      島根県立産業交流会館(島根県)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] マウス骨格筋in vivo イメージングによるサルコメア構造と微小管系の可 視化2012

    • Author(s)
      小林琢也、茅元司、樋口秀男
    • Organizer
      ナノ学会第10 回大会
    • Place of Presentation
      大阪大学(大阪府)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 量子ドットを用いたマ ウス耳内における白血球内小胞運動の非侵襲イメージ ング2012

    • Author(s)
      菊島健児、喜多清、樋口秀男
    • Organizer
      ナノ学会第10 回大会
    • Place of Presentation
      大阪大学(大阪府)
    • Related Report
      2012 Annual Research Report
  • [Presentation] In vivo imaging of single molecules in cancer cells of xenograft model under noninvasive condition2012

    • Author(s)
      喜多清、菊島健児、樋口秀男
    • Organizer
      第71 回日本癌学会学術総会
    • Place of Presentation
      札幌教育文化会館(北海道)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Non-invasive in vivo imaging of vesicle movement in neutrophils in mouse ear2012

    • Author(s)
      菊島健児、喜多清、樋口秀男
    • Organizer
      第50 回日本生物物理学会年会
    • Place of Presentation
      名古屋大学(愛知県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Single molecule biophysics in an in vivo and in vitro2012

    • Author(s)
      Higuchi H.
    • Organizer
      Japan-Taiwan joint symposium
    • Place of Presentation
      京都大学(京都府)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 非侵襲マウス耳介内での量子ドットを用いた白血球内の小胞運動解析2012

    • Author(s)
      菊島健児
    • Organizer
      生体運動班会議
    • Place of Presentation
      筑波大学(茨城県)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 高輝度量子ドットを用いたマウス耳内血管の非侵襲イメージング2011

    • Author(s)
      菊島健児
    • Organizer
      ナノ学会
    • Place of Presentation
      北海道大学(北海道)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Imaging of mouse ear blood vessel under non-invasive conditions with high-fluorescence quantum dots2011

    • Author(s)
      Kikushima
    • Organizer
      生物物理学会
    • Place of Presentation
      兵庫県立大学(兵庫県)
    • Related Report
      2011 Annual Research Report
  • [Book] 少数性生物学2017

    • Author(s)
      茅 元司
    • Total Pages
      178
    • Publisher
      日本評論社
    • Related Report
      2015 Annual Research Report
  • [Book] 1分子生物学2014

    • Author(s)
      樋口秀男,多田隈尚史
    • Total Pages
      304
    • Publisher
      化学同人
    • Related Report
      2014 Annual Research Report
  • [Book] 先端バイオマテリアルハンドブック2012

    • Author(s)
      樋口秀男、権田幸祐
    • Total Pages
      656
    • Publisher
      NTS 出版
    • Related Report
      2012 Annual Research Report
  • [Book] Handbook of Dynein2012

    • Author(s)
      Y Toyoshima and H. Higuchi
    • Total Pages
      20
    • Publisher
      Motile and Enzymatic properties of native dynein molecules
    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] 共焦点顕微鏡画像システム2011

    • Inventor(s)
      :樋口秀男、下澤東吾
    • Industrial Property Rights Holder
      :樋口秀男、下澤東吾
    • Industrial Property Rights Type
      特許
    • Filing Date
      2011-05-31
    • Related Report
      2011 Annual Research Report
    • Overseas

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Published: 2011-08-01   Modified: 2019-07-29  

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