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Mathematical model for cellular dysfunctions caused by failure in post-translational signal transduction

Planned Research

Project AreaRegulation of signal transduction by post-translational modifications and its pathogenic dysregulation
Project/Area Number 22117008
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 InstitutionThe University of Tokyo

Principal Investigator

ICHIKAWA Kazuhisa  東京大学, 医科学研究所, 特任教授 (20343626)

Project Period (FY) 2010-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥50,050,000 (Direct Cost: ¥38,500,000、Indirect Cost: ¥11,550,000)
Fiscal Year 2014: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2013: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2012: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2011: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Fiscal Year 2010: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
KeywordsNF-kappaB / stress granule / cancer / computer simulation / spatio-temporal dynamics / 細胞シミュレーション / NF-kB / 核移行 / 振動 / ストレス顆粒 / 反応拡散 / NF-κB核移行 / ユビキチン化 / TRAF6 / MEKK3 / IKK / A-Cell / stochastic simulation
Outline of Final Research Achievements

Dysfunction in intracellular signal transduction is a cause of many diseases. Majority of computational signal transduction research has been focused on pathways. Since a cell is 3D entity, we tested the effect of spatial parameters on the signal transduction.
First we found that oscillation of transcription factor NF-kB was regulated by diffusion coefficient, nuclear transport, and nuclear/cytoplasmic volume ratio, and in addition, while diffusion coefficient and export for mRNA from the nucleus regulated persistency of NF-kB oscillation, IkB import to the nucleus exclusively regulated oscillation frequency. Second, we found that the fusion of stress granules (SGs) was important for their dynamics, and simulation predicted gamma distribution of SG size, which was confirmed by experiments.

Report

(6 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (55 results)

All 2015 2014 2013 2012 2011 2010 Other

All Journal Article (18 results) (of which Peer Reviewed: 16 results,  Open Access: 4 results,  Acknowledgement Compliant: 4 results) Presentation (27 results) (of which Invited: 17 results) Book (3 results) Remarks (7 results)

  • [Journal Article] Spatio-temporal dynamics and mechanisms of stress granule assembly2015

    • Author(s)
      Ohshima, D., Arimoto-Matsuzaki, K., Tomida, T., Takekawa, M., and Ichikawa, K.
    • Journal Title

      PLoS Comp.Biol.

      Volume: 印刷中

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Regulation of NF-kB oscillation by nuclear transport: Mechanisms determining persistency and frequency of oscillation2015

    • Author(s)
      Ohshima, D. and Ichikawa, K.
    • Journal Title

      PLoS ONE

      Volume: 印刷中

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Dynamic Regulation of a Cell Adhesion Protein Complex Including CADM1 by Combinatorial Analysis of FRAP with Exponential Curve-fitting2015

    • Author(s)
      Sakurai-Yageta, M., Maruyama,T., Suzuki, T., Ichikawa, K., and Murakami, Y.
    • Journal Title

      PLoS ONE

      Volume: 10 Issue: 3 Pages: 0116637-0116637

    • DOI

      10.1371/journal.pone.0116637

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of nuclear NF-kB oscillation by a diffusion coefficient and its biological implications2014

    • Author(s)
      Ohshima, D. and Ichikawa, K.
    • Journal Title

      PLoS ONE

      Volume: 9 Issue: 10 Pages: e109895-e109895

    • DOI

      10.1371/journal.pone.0109895

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Regulation of signal transduction by spatial parameters: a case in NF-kB oscillation2014

    • Author(s)
      Ichikawa, K., Ohshima, D., and Sagara, H.
    • Journal Title

      IET Systems Biology

      Volume: 9 Issue: 2 Pages: 41-51

    • DOI

      10.1049/iet-syb.2013.0020

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Spatial chaos and complexity in the intracellular space of cancer and normal cells2013

    • Author(s)
      Pham, T.D., and Ichikawa, K.
    • Journal Title

      Theoretical Modeling and Medical Biology

      Volume: 10 Issue: 1 Pages: 62-62

    • DOI

      10.1186/1742-4682-10-62

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of NF-kB Oscillation by Spatial Parameters in True Intracellular Space (TiCS)2013

    • Author(s)
      Ohshima, D., Sagara, H., and Ichikawa, K.
    • Journal Title

      2013 International Symposium on Computational Models for Life Sciences, AIP Conf.Proc.

      Volume: 1559 Pages: 5-11

    • DOI

      10.1063/1.4824990

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Critical role of transient activity of MT1-MMP for ECM degradation in invadopodia2013

    • Author(s)
      Watanabe, A., Hoshino D., Koshikawa, N., Seiki, M., Suzuki, T., and Ichikawa, K.
    • Journal Title

      PLoS Comp.Biol.

      Volume: 9 Issue: 6

    • DOI

      10.1371/annotation/b41ed85a-11d1-483a-a7ac-9d06f0c8669a

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] シミュレーションによるがん浸潤初期過程の動的理解2013

    • Author(s)
      市川一寿
    • Journal Title

      実験医学

      Volume: 31 Pages: 2932-2938

    • Related Report
      2013 Annual Research Report
  • [Journal Article] 転写因子NF-kBの振動パターンに大きな影響を与える3次元細胞内空間構造2013

    • Author(s)
      大島大輔・市川一寿
    • Journal Title

      生化学

      Volume: 85 Pages: 430-437

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Control and inhibition analysis of complex formation processes.2012

    • Author(s)
      Saitou T, Itano K, Hoshino D, Koshikawa N, Seiki M, Ichikawa K, Suzuki T.
    • Journal Title

      Theor Biol Med Model.

      Volume: 3 Issue: 1 Pages: 33-33

    • DOI

      10.1186/1742-4682-9-33

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles of spatial parameters on the oscillation of nuclear NF-#61547;B: computer simulations of a 3D spherical cell.2012

    • Author(s)
      Oshima, D
    • Journal Title

      PLoS ONE

      Volume: 7 Issue: 10 Pages: e46911-e46911

    • DOI

      10.1371/journal.pone.0046911

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reaction diffusion equation with non-local term arises as a mean field limit of the master equation2012

    • Author(s)
      Ichikawa, K., Rouzimaimaiti, M., (Suzuki, T.)
    • Journal Title

      Discrete and Continuous Dynamical Systems Series S

      Volume: 5 Issue: 1 Pages: 105-126

    • DOI

      10.3934/dcdss.2012.5.115

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mathematical modeling of invadopodia formation2012

    • Author(s)
      T.Saitou, M.Rouzimaimaiti, N.Koshikawa, M.Seiki, K.Ichikawa, T.Suzuki
    • Journal Title

      J.Theoretical Biology

      Volume: 298 Pages: 138-146

    • DOI

      10.1016/j.jtbi.2011.12.018

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Establishment and validation of computational model for MT1-MMP dependent ECM degradation and intervention strategies2012

    • Author(s)
      Hoshino, D., Koshikawa, N., Suzuki, T., Quaranta, V., Weaver, A.M., (Seiki, M.), Ichikawa, K.
    • Journal Title

      PLoS Comp.Biol.

      Volume: 8 Issue: 4 Pages: e1002479-e1002479

    • DOI

      10.1371/journal.pcbi.1002479

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 核内NF-kBの振動とその制御の数理モデル2012

    • Author(s)
      大島大輔、(市川一寿)
    • Journal Title

      実験医学増刊 シグナル伝達研究最前線2012

      Volume: 30 Pages: 709-715

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Localized activation of proteins in a free intracellular space: dependence of cellular morphologies and reaction schemes2011

    • Author(s)
      Kazuhisa Ichikawa
    • Journal Title

      BioSystems

      Volume: 105 Pages: 173-180

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stochastic simulation of biological reactions, and its applications for studying actin polymerization2010

    • Author(s)
      Kazuhisa Ichikawa
    • Journal Title

      Physical Biology

      Volume: 7 Pages: 46010-46010

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Oscillation Pattern of Transcription Factor NF-kB Regulated by Spatial Parameters2014

    • Author(s)
      K. Ichikawa
    • Organizer
      数学協働プログラム、科学技術振興機構/統計数理研究所
    • Place of Presentation
      大阪 大阪大学豊中キャンパス
    • Year and Date
      2014-11-01
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Synergistic effect of blocking cancer cell invasion revealed by computer simulations2014

    • Author(s)
      K. Ichikawa
    • Organizer
      2014 NIMS Hot Topics Workshops, “Application of ecological and mathematical theory to cancer: new challenges”
    • Place of Presentation
      韓国 太田市
    • Year and Date
      2014-05-12 – 2014-05-15
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Analysis of regulatory mechanisms of transcription factor NF-kB in 3D spherical computational cell model2013

    • Author(s)
      D. Ohshima and K. Ichikawa
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] Regulation of NF-kB Oscillation by Spatial Parameters in True Intracellular Space (TIS)2013

    • Author(s)
      K. Ichikawa, H. Sagara and D. Ohshima
    • Organizer
      CMLS-13
    • Place of Presentation
      Sidney, Australia
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Characterization of cancer and normal intracellular images by the power law of a fuzzy partition functional2013

    • Author(s)
      T.D. Pham, K. Ichikawa
    • Organizer
      Int. Conf. Image Analysis and Recognition (ICIAR 2013)
    • Place of Presentation
      Povoa de Varzim, Portuga
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] がん浸潤初期過程の研究におけるシミュレーションと実験の相互作用2013

    • Author(s)
      市川一寿
    • Organizer
      文部科学省・科学研究費補助金・新学術領域研究「修飾シグナル病」、若手ワークショップ
    • Place of Presentation
      伊香保
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Predictive dynamic regulation of MT1-MMP at invadopodia by mathematical modeling and computer simulation2013

    • Author(s)
      K. Ichikawa
    • Organizer
      Tsukuba Global Science Week 2013
    • Place of Presentation
      つくば
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] がんの浸潤最初期ダイナミクスの理解によって転移抑制を目指す2013

    • Author(s)
      市川一寿
    • Organizer
      応用数理学会2013年度年会オーガナイズドセッション
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 細胞内3次元空間がNF-kBの振動に与える影響2013

    • Author(s)
      市川一寿
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Signal Transduction in Real Intracellular Space2013

    • Author(s)
      D. Ohshima, H. Sagara, T.D. Pham, K. Ichikawa
    • Organizer
      35th IEEE EMBC Full-day Workshop on Current Challenging Image Analysis and Information Processing in Life Sciences
    • Place of Presentation
      Osaka
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Segmentation of Endoplasmic Reticulum in Intracellular Space2013

    • Author(s)
      N. Nguyen-Thanh, T.D. Pham, H. Sagara, K. Ichikawa
    • Organizer
      35th IEEE EMBC Full-day Workshop on Current Challenging Image Analysis and Information Processing in Life Sciences
    • Place of Presentation
      Osaka
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Computational simulation revealed critical spatial parameters that change oscillation pattern of nuclear NF-kB2013

    • Author(s)
      Kazuhisa Ichikawa
    • Organizer
      1st International Symposium on Protein Modifications in Pathogenic Dysregulation of Signaling
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] ストレス顆粒の形成・維持・消滅の力学2012

    • Author(s)
      市川一寿
    • Organizer
      応用数理学会2012年度年会
    • Place of Presentation
      稚内
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 転写因子NF-kB振動の数理モデル2012

    • Author(s)
      大島大輔、井上純一郎、(市川一寿)
    • Organizer
      応用数理学会2012年度年会
    • Place of Presentation
      稚内
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] MT1-MMP and the dynamics of invadopodia for ECM degradation2012

    • Author(s)
      市川一寿
    • Organizer
      MT1-MMPシンポジウム
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 浸潤突起へのMT1-MMP輸送によるECM分解促進のシミュレーションモデルとその解析2012

    • Author(s)
      渡部綾子、(市川一寿)
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] 細胞内空間パラメータは転写因子NF-kBの核内振動を制御する:3Dシミュレーションによる解析2012

    • Author(s)
      大島大輔、井上純一郎、(市川一寿)
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] A new method of stochastic simulation and its application to the reorganization of actin filaments in invadopodia2011

    • Author(s)
      Kazuhisa Ichikawa
    • Organizer
      AACR-NCI Conference on Systems Biology
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2011-03-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] タンパク複合体シミュレーションの基礎とTRAF6複合体におけるNF-κB活性化2011

    • Author(s)
      市川一寿
    • Organizer
      文部科学省・科学研究費補助金・新学術領域研究「修飾シグナル病」第一回公開シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2011-01-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] Significance of rapid turnover of MT1-MMP for the degradation of ECM: an approach by computer simulation2011

    • Author(s)
      Ichikawa, K.
    • Organizer
      The Third CREST-SBM International Conference, Mathematical Methods in Cancer Cell Biology
    • Place of Presentation
      Hiroshima
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] Modeling and Simulation of the Initial Step in Cancer Invasion2011

    • Author(s)
      Ichikawa, K.
    • Organizer
      2011 International Symposium on Computational Models for Life Sciences
    • Place of Presentation
      Toyama
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] The role of vesicle-trafficked MT1-MMP in ECM degradation: A computer simulation2011

    • Author(s)
      Watanabe, A. and (Ichikawa, K.)
    • Organizer
      Metabolism and Cancer, AACR Special Conference
    • Place of Presentation
      Baltimore, USA
    • Related Report
      2011 Annual Research Report
  • [Presentation] A computational simulation of nuclear transport of NF-kB in three-dimensional model including Rel-A phosphorylation2011

    • Author(s)
      Oshima, D. and (Ichikawa K.)
    • Organizer
      Metabolism and Cancer, AACR Special Conference
    • Place of Presentation
      Baltimore, USA
    • Related Report
      2011 Annual Research Report
  • [Presentation] Oscillation of transcription factor NF-kB Causal function or inevitable consequence?: An implication from computer simulations2011

    • Author(s)
      Ichikawa, K.
    • Organizer
      Workshop on “Dynamics and molecular basis of post-translational modifications and cell signaling networks : Interdisciplinary approaches to understanding biological systems
    • Place of Presentation
      Yokohama
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] A computer simulation of ECM degradation by Vesicle-trafficked MT1-MMP in invadopodia2011

    • Author(s)
      Watanabe, A. and (Ichikawa, K.)
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2011 Annual Research Report
  • [Presentation] In Silico Spatio-temporal simulation of NF-kB oscillation2011

    • Author(s)
      Oshima, D. and (Ichikawa K.)
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2011 Annual Research Report
  • [Presentation] Bottom up modeling of protein dynamics in invadopodia2010

    • Author(s)
      Kazuhisa Ichikawa
    • Organizer
      International Workshop on Mathematics for Biology
    • Place of Presentation
      Pohang, Republic of Korer
    • Year and Date
      2010-07-12
    • Related Report
      2010 Annual Research Report
  • [Book] 「シグナル伝達の数理モデル」、分子消化器病2014

    • Author(s)
      大島大輔、市川一寿
    • Total Pages
      7
    • Publisher
      先端医学社
    • Related Report
      2014 Annual Research Report
  • [Book] Nuclear Boundary and Pore Detection in SEM Images, in “Biomedical Informatics and Technology”, Eds. Tuan D. Pham, Kazuhisa Ichikawa, Mayumi Oyama-Higa, and Xiaoyi Jiang2014

    • Author(s)
      Isabel Schwende, Tuan D. Pham, and Kazuhisa Ichikawa
    • Total Pages
      13
    • Publisher
      Springer-Verlag Berlin Heidelberg
    • Related Report
      2014 Annual Research Report
  • [Book] Nuclear Boundary and Pore Detection in SEM Images2014

    • Author(s)
      Isabel Schwende, Tuan D. Pham, and Kazuhisa Ichikawa
    • Total Pages
      13
    • Publisher
      Springer-Verlag Berlin Heidelberg
    • Related Report
      2013 Annual Research Report
  • [Remarks] 東京大学医科学研究所腫瘍数理分野ホームページ

    • URL

      http://www.ims.u-tokyo.ac.jp/mathcancer/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 新学術領域「修飾シグナル病」ホームページ

    • URL

      http://shushoku-signal.com/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 東京大学医科学研究所腫瘍数理分野ホームページ

    • URL

      http://www.ims.u-tokyo.ac.jp/mathcancer/index.html

    • Related Report
      2012 Annual Research Report
  • [Remarks] 新学術領域「修飾シグナル病」ホームページ

    • URL

      http://shushoku-signal.com/

    • Related Report
      2012 Annual Research Report
  • [Remarks] 東京大学医科学研究所腫瘍数理分野ホームページ

    • URL

      http://www.ims.u-tokyo.ac.jp/mathcancer/index.html

    • Related Report
      2011 Annual Research Report
  • [Remarks] 新学術領域「修飾シグナル病」ホームページ

    • URL

      http://shushoku-signal.com/

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.ims.u-tokyo.ac.jp/mathcancer/index.html

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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