Time-lapse image analysis of the local membrane environment surrouding the insulin receptor with an information science approach

• Project/Area Number: 16K16153
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Life / Health / Medical informatics
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Takemoto Satoko 国立研究開発法人理化学研究所, 光量子工学研究センター, 研究員 (00450403)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 画像解析 / 細胞内ロジスティクス / 細胞膜 / インスリン受容体 / 可視化 / 膜流動性 / 領域分割 / 画像処理 / 画像認識

Outline of Final Research Achievements

In this study, in order to understand how the membrane domain surrounding signaling molecules changes during insulin signaling, we have developed an image analysis procedure. The procedure includes automatic detection for insulin receptor from noisy time-lapse images, measuring membrane fluidity based on Generalized polarization (GP) value, and visualization of GP value using Zero-mean normalized cross correlation (ZNCC).
Our results reveals that the membrane fluidity of local environment surrounding the insulin receptor increased upon insulin stimulation. Furthermore, we found the local membrane environment of the insulin receptor was quite dynamic and heterogeneous. These results suggest that the insulin receptor has distinct local membrane environment from the general plasma membrane.

Academic Significance and Societal Importance of the Research Achievements

本研究はこれまで観察が難しかった細胞膜上のインスリン受容体周辺について、初めてタイムラプス観察画像を取得し、その動態を画像解析したものである。これは、インスリン受容体を環境感受性の蛍光プローブで直接ラベルする観察系が、研究協力者らによって確立されたことによる。本研究によって大量のタイムラプス観察画像の自動解析法が確立できたことで、これまで不明であった受容体周辺の膜流動性についての定量解析が可能となった。結果として、インスリン刺激時の受容体周辺の膜流動性の変化や空間分布の不均一性が明らかになるなど、病態の発生原因の解明研究の促進に寄与することができたと考えている。

Research Products

• [Int'l Joint Research] ジュネーブ大学(スイス)
• [Int'l Joint Research] ジュネーブ大学/NCCR(スイス)
• [Int'l Joint Research] ジュネーブ大学(スイス)
• [Int'l Joint Research] ジュネーブ大学(スイス)
• [Journal Article] An end-to-end CNN and LSTM network with 3D anchors for mitotic cell detection in 4D microscopic images and its parallel implementation on multiple GPUs (2020)
  • Author(s): T. Kitrungrotsakul, X.-X Han, Y. Iwamoto, S. Takemoto, H. Yokota, S. Ipponjima, T. Nemoto, X. Wei, and Y.-W. Chen,
  • Journal Title: Neural Computing and Applications Volume: Vol. 32 Issue: 10 Pages: 5669-5679
  • DOI: 10.1007/s00521-019-04374-8
  • Peer Reviewed / Open Access
• [Journal Article] A Cascade of 2.5D CNN and Bidirectional CLSTM Network for Mitotic Cell Detection in 4D Microscopy Image (2019)
  • Author(s): Titinunt Kitrungrotsakul, Yutaro Iwamoto, Xian-Hau Han, Satoko Takemoto, Hideo Yokota, Sari Ipponjima, Tomomi Nemoto, Xiong Wei, Yen-Wei Chen
  • Journal Title: proc. IEEE/ACM Transactions on Computational Biology and Bioinformatics Volume: － Issue: 2 Pages: 1-9
  • DOI: 10.1109/tcbb.2019.2919015
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A statistical image analysis framework for pore-free islands derived from heterogeneity distribution of nuclear pore complexes (2017)
  • Author(s): Mimura Yasuhiro、Takemoto Satoko、Tachibana Taro、Ogawa Yutaka、Nishimura Masaomi、Yokota Hideo、Imamoto Naoko
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 16315-16315
  • DOI: 10.1038/s41598-017-16386-2
  • Peer Reviewed / Open Access
• [Presentation] Receptor-linked environment-sensitive probe reveals the heterogeneity of local-membrane environment surrounding the insulin receptor (2019)
  • Author(s): 27.M. Umebayashi, S. Takemoto, L. Reymond, M. Sundukova, A. Bucci, P.A. Heppenstall, H. Yokota, K. Johnsson, H. Riezman
  • Organizer: International Conference on the Bioscience of Lipids
  • Int'l Joint Research
• [Presentation] 画像処理法の決定支援システム: Sommelier (2019)
  • Author(s): 竹本 智子, 横田 秀夫
  • Organizer: 理化学研究所・広島大学合同公開シンポジウム「イメージングから理論」
• [Presentation] A cloud-based communication platform for image-based brain research (2019)
  • Author(s): 19.M. Morita, S. Takemoto, M. Nishimura, Y. Morii, M. Maeda, Y. Okumura, Y. Yamaguchi, and H. Yokota
  • Organizer: International Symposium of Brain/MINDS
  • Int'l Joint Research
• [Presentation] Bioimage Processing (2019)
  • Author(s): 20.H. Yokota, S. Yoshizawa, S. Takemoto, M. Morita, T. Sera, M. Nishimura, Y. Tsujimura, S. Nakamura, and T. Michikawa
  • Organizer: Resonance Bio International Symposium
  • Int'l Joint Research
• [Presentation] Cloud-based image processing system: RBICP (2019)
  • Author(s): 24.M. Morita, M. Nishimura, S. Takemoto, Y. Tsujimura, and H. Yokota
  • Organizer: Resonance Bio International Symposium
  • Int'l Joint Research
• [Presentation] An End-to-end CNN and CLSTM Network with 3D Anchors for Mitotic Cell Detection in 4D Microscopic Image (2019)
  • Author(s): 25.Y.-W. Chen, T. Kitrungrotsakul, X.-H. Han, Y. Iwamoto, J. Liu, S. Takemoto, H. Yokota, S. Ipponjima, and T. Nemoto
  • Organizer: Resonance Bio International Symposium
  • Int'l Joint Research
• [Presentation] A Cascade of CNN and LSTM Network with 3D Anchors for Mitotic Cell Detection in 4D Microscopic Image. (2019)
  • Author(s): Kitrungrotsakul, Titinunt & Iwamoto, Yutaro & Han, Xian-Hau & Takemoto, Satoko & Yokota, Hideo & Ipponjima, Sari & Nemoto, Tomomi & Xiong, Wei & Chen, Yen-Wei.
  • Organizer: ICASSP 2019 - 2019 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP)
  • Int'l Joint Research
• [Presentation] 画像処理法の決定支援システムSommelier (2018)
  • Author(s): 竹本 智子, 森田 正彦, 西村 将臣, 横田 秀夫
  • Organizer: 画像センシングシンポジウム (SSII)
• [Presentation] Probing the local membrane environment of the human insulin receptor (2018)
  • Author(s): M. Umebayashi, L. Reymond, S. Takemoto, H. Yokota, M. Sundokova, K. Johnsson, H. Riezman
  • Organizer: 第70回日本細胞生物学会
• [Presentation] インスリン受容体近傍の局所的な膜動態の観察 (2018)
  • Author(s): 梅林 美和, Luc Reymond, 竹本 智子, 横田 秀夫, Kai Johnsson, Howard Reizman
  • Organizer: 第60回日本脂質生化学会
• [Presentation] Probing the local environment of the human insulin receptor (2018)
  • Author(s): M. Umebayashi, L. Reymond, R. Hovius, S. Takemoto, H. Yokota, M. Sundukova, A. Bucci, P. Heppenstall, K. Johnsoon, H. Riezman
  • Organizer: NCCR seminar
  • Int'l Joint Research
• [Presentation] Sommelier: A system for performance evaluation of image segmentation methods toward better objectivity of cell image analysis (2017)
  • Author(s): S. Takemoto, M. Umebayashi, M. Morita, H. Riezman, and H. Yokota
  • Organizer: Taiwan-Japan Joint Meeting on Bioimaging for Young Researchers
  • Int'l Joint Research
• [Presentation] Performance evaluation of image segmentation methods for better objectivity of cell image analysis (2017)
  • Author(s): S. Takemoto
  • Organizer: NCCR Special Lecture series
  • Invited
• [Presentation] 画像処理法の性能評価システムを用いた細胞膜認識手順の自動化 (2017)
  • Author(s): 竹本智子, 梅林美和, 森田正彦, Riezman Howard, 横田秀夫
  • Organizer: 第23回画像センシングシンポジウム（SSII2017）
• [Presentation] 人間の領域認識の模倣を目指す画像処理システムの開発 (2016)
  • Author(s): 竹本智子, 横田秀夫
  • Organizer: Bioimage Informatics Workshop 2016
  • Place of Presentation: 大阪大学吹田キャンパス 銀杏会館
  • Year and Date: 2016-06-22