TOGASHI Yuichi {Theoretical, Computational} Biophysics Researcher 　冨樫 祐一　　研究者＠｛理論,計算｝生物物理

Research Interests

Small Number and Minority Issues in Biological Systems

In biochemical systems, there are lots of chemical species, but the total amount per cell is not large; i.e., some chemicals are rare. An extreme case is genome DNA; there are only 1 to a few copies in a cell. We investigate effects of finite-size fluctuations or discreteness in numbers of molecules for such rare species.

After the projects "Spying Minority in Biological Phenomena" (2011-2016) and "Singularity Biology" (2018-2023), we are still in collaboration also with experimentalists. For further information, please see the project web-sites.

Dynamical Properties of Molecular Machines

Biological cells utilize a variety of molecular machines (enzymes, motors, pumps and channels, etc.) for their activities. In these molecules, the function is often coupled with their motion (conformational changes). We study their dynamical properties by molecular dynamics simulations, using either or combination of all-atom and coarse-grained modeling, to understand their operation principles.

Modeling of Molecular Machinery in the Cell

We are currently modeling systems consisting of molecular machines, as an expansion of reaction diffusion systems, taking into account features of the intracellular environment, e.g.:
- Excluded volume effects and congestion of molecules,
- Complex/complicated membrane structures,
- Active transport, which itself is driven by molecular machines.

Particularly, we are interested in the relationship between the structure and function of the chromatin strucure (DNA-protein complex) in the cell nucleus, and also codon recognition mechanisms in ribosomes.

Application of Biological Mechanisms to Artificial Systems

We believe that the very nature of living systems is information processing, or "computation". In future, once we have described operation and design principles of a certain biological system in a theoretical or algorithmic way, it is highly expected that we can create an artificial device performing the same or similar function but made from different materials. Such a system may transcend the limitations of natural biomolecules.

Publications

• T. Kameda, A. Awazu, Y. Togashi,
  "Molecular dynamics analysis of biomolecular systems including nucleic acids",
  Biophys. Physicobiol. 19, e190027 (2022).
• Y. Fujita, T. Kameda, C. R. Singh, W. Pepper, A. Cecil, M. Hilgers, M. Thornton, I. Asano, C. Moravek, Y. Togashi, H. Saito, K. Asano,
  "Translational recoding by chemical modification of non-AUG start codon ribonucleotide bases",
  Sci. Adv. 8, eabm8501 (2022).
• Y. Togashi,
  "Multiscale modeling of chromatin considering the state and shape of molecules", Advances in Computational Modeling and Simulation (R. Srinivas, R. Kumar, M. Dutta eds.), Springer Nature Singapore, 171 (2022).
• T. Kameda, K. Asano, Y. Togashi,
  "Free energy landscape of RNA binding dynamics in start codon recognition by eukaryotic ribosomal pre-initiation complex",
  PLoS Comput. Biol. 17, e1009068 (2021).
• T. Kameda, M. M. Suzuki, A. Awazu, Y. Togashi,
  "Structural dynamics of DNA depending on methylation pattern",
  Phys. Rev. E 103, 012404 (2021).
• 亀田 健, 粟津 暁紀, 冨樫 祐一,
  「過渡的に生じる中間体ヌクレオソームにおけるヒストンテール動態の解析」,
  生物物理 60, 288 (2020).
• S. Shinkai, M. Nakagawa, T. Sugawara, Y. Togashi, H. Ochiai, R. Nakato, Y. Taniguchi, S. Onami,
  "PHi-C: deciphering Hi-C data into polymer dynamics",
  NAR Genom. Bioinform. 2, lqaa020 (2020).
• T. Kameda, A. Awazu, Y. Togashi,
  "Histone tail dynamics in partially disassembled nucleosomes during chromatin remodeling",
  Front. Mol. Biosci. 6, 133 (2019).
• R. Amyot, Y. Togashi, H. Flechsig,
  "Analyzing fluctuation properties in protein elastic networks with sequence-specific and distance-dependent interactions",
  Biomolecules 9, 549 (2019).
• Y. Togashi,
  "Modeling of nanomachine/micromachine crowds: interplay between the internal state and surroundings",
  J. Phys. Chem. B 123, 1481-1490 (2019).
• Y. Togashi, H. Flechsig,
  "Coarse-grained protein dynamics studies using elastic network models",
  Int. J. Mol. Sci. 19, 3899 (2018).
• T. Nagai, Y. Togashi eds.
  "Minorities and Small Numbers from Molecules to Organisms in Biology: Toward a New Understanding of Biological Phenomena", Springer Singapore (2018).
• H. Flechsig, Y. Togashi,
  "Designed elastic networks: models of complex protein machinery",
  Int. J. Mol. Sci. 19, 3152 (2018).
• M. Yanagawa, M. Hiroshima, Y. Togashi, M. Abe, T. Yamashita, Y. Shichida, M. Murata, M. Ueda, Y. Sako,
  "Single-molecule diffusion-based estimation of ligand effects on G protein-coupled receptors",
  Sci. Signal. 11, eaao1917 (2018).
• Y. Togashi, S. Shinkai, T. Komatsuzaki,
  "Small Numbers and Individuality of Molecules"
  (in Japanese; 「少数と個性―分子の数と生命らしさ」),
  Experimental Medicine (実験医学) 35, 3190-3196 (2017). [Publisher's site]
• E. Rolls, Y. Togashi, R. Erban,
  "Varying the Resolution of the Rouse Model on Temporal and Spatial Scales: Application to Multiscale Modelling of DNA Dynamics",
  Multiscale Model. Simul. 15, 1672-1693 (2017). [Link to the article] [Preprint (arXiv:1607.08062)]
• M. Nakagawa, S. Onaka, Z. Luo, Y. Togashi,
  「非一様な多機能触媒反応系における少数分子成分効果」(in Japanese),
  RIMS Kôkyûroku (京都大学数理解析研究所講究録) 2028, 120-133 (in Y. Sato ed., The Theory of Random Dynamical Systems and Its Applications) (2017). [Link to the article]
• S. Shinkai, T. Nozaki, K. Maeshima, Y. Togashi,
  "Bridging the Dynamics and Organization of Chromatin Domains by Mathematical Modeling",
  Nucleus 8, 353-359 (2017). [Link to the article (Free)]
• T. Nagai, Y. Togashi, eds.
  "Spying Minority in Biological Phenomena", Nippon Hyoron sha (in Japanese);
  永井健治, 冨樫祐一 編, 「少数性生物学」, 日本評論社 (2017). [Publisher's site]
• T. Kameda, S. Isami, Y. Togashi, H. Nishimori, N. Sakamoto, A. Awazu,
  "The 1-Particle-per-k-Nucleotides (1PkN) Elastic Network Model of DNA Dynamics with Sequence-Dependent Geometry",
  Front. Physiol. 8, 103 (2017). [Link to the article (Free)]
• N. Tochio, K. Umehara, J. Uewaki, H. Flechsig, M. Kondo, T. Dewa, T. Sakuma, T. Yamamoto, T. Saitoh, Y. Togashi, S. Tate,
  "Non-RVD Mutations that Enhance the Dynamics of the TAL Repeat Array along the Superhelical Axis Improve TALEN Genome Editing Efficacy",
  Sci. Rep. 6, 37887 (2016). [Link to the article (Free)] [日本語説明]
• S. Shinkai, T. Nozaki, K. Maeshima, Y. Togashi,
  "Dynamic Nucleosome Movement Provides Structural Information of Topological Chromatin Domains in Living Human Cells",
  PLoS Comput. Biol. 12, e1005136 (2016). [Link to the article (Free)] [日本語説明]
• Y. Togashi,
  "Screening for Mechanical Responses of Proteins Using Coarse-grained Elastic Network Models",
  NOLTA, IEICE 7, 190-201 (2016). [Link to the article (Free)]
• M. Nakagawa, Y. Togashi,
  "An Analytical Framework for Studying Small-Number Effects in Catalytic Reaction Networks: A Probability Generating Function Approach to Chemical Master Equations",
  Front. Physiol. 7, 89 (2016). [Link to the article (Free)]
• M. Ishibashi, Y. Miyanaga, S. Matsuoka, J. Kozuka, Y. Togashi, T. Kinashi, M. Ueda,
  "Integrin LFA-1 Regulates Cell Adhesion via Transient Clutch Formation",
  Biochem. Biophys. Res. Commun. 464, 459-466 (2015). [Link to the article (Free)]
• Y. Togashi, V. Casagrande,
  "Spatiotemporal Patterns Enhanced by Intra- and Inter-molecular Fluctuations in Arrays of Allosterically Regulated Enzymes",
  New J. Phys. 17, 033024 (2015). [Link to the article (Free)]
• R. Erban, A. Funahashi, M. Herajy, T. J. Kobayashi, K. Takahashi, Y. Togashi,
  "DNA Structural Dynamics (Team 5)",
  Dagstuhl Reports 4, 191-194 (in Gilbert, D., et al. eds., Multiscale Spatial Computational Systems Biology (Dagstuhl Seminar 14481)) (2015). [Link to the article (Free)]
• Y. Togashi,
  "Spying “Minorities” in the Cell",
  Dagstuhl Reports 4, 165-166 (in Gilbert, D., et al. eds., Multiscale Spatial Computational Systems Biology (Dagstuhl Seminar 14481)) (2015). [Link to the article (Free)]
• Y. Togashi,
  "Theoretical Studies of Reaction Networks Involving Small Numbers of Molecules"
  (in Japanese; 「少数分子反応系理論・少数性生物学」),
  Seitai no Kagaku (生体の科学) 65, 450-451 (2014). [Link to the article]
• S. Shinkai, Y. Togashi,
  "Energetics of Single Active Diffusion Trajectories"
  Europhys. Lett. 105, 30002 (2014). [Link to the article (Free)]
• M. Iwaki, L. Marcucci, Y. Togashi, T. Yanagida,
  "Single molecule and collective dynamics of motor protein coupled with mechano-sensitive chemical reaction", Engineering of Chemical Complexity (A. S. Mikhailov, G. Ertl eds.), World Scientific, Chapter 4, 79 (2013).
• M. Morimatsu, Y. Togashi, S. Nishikawa, M. Sugawa, A. H. Iwane, T. Yanagida
  "Spontaneous Structural Changes in Actin Regulate G-F Transformation"
  PLOS ONE 7, e45864 (2012). [Link to the article (Free)]
• M. Düttmann, M. Mittnenzweig, Y. Togashi, T. Yanagida, A. S. Mikhailov,
  "Complex Intramolecular Mechanics of G-actin ― An Elastic Network Study"
  PLOS ONE 7, e45859 (2012). [Link to the article (Free)]
• M. Düttmann, Y. Togashi, T. Yanagida, A. S. Mikhailov,
  "Myosin-V as a Mechanical Sensor: An Elastic Network Study"
  Biophys. J. 102, 542-551 (2012). [Link to the article]
• C. Echeverria, Y. Togashi, A. S. Mikhailov, R. Kapral,
  "A Mesoscopic Model for Protein Enzymatic Dynamics in Solution"
  Phys. Chem. Chem. Phys. 13, 10527-10537 (2011). [Link to the article]
• Y. Togashi, T. Yanagida, A. S. Mikhailov,
  "Nonlinearity of Mechanochemical Motions in Motor Proteins"
  PLoS Comput. Biol. 6, e1000814 (2010). [Link to the article (Free)] [Preprint (1006.1439)]
• A. Cressman, Y. Togashi, A. S. Mikhailov, R. Kapral,
  "Mesoscale Modeling of Molecular Machines: Cyclic Dynamics and Hydrodynamical Fluctuations",
  Phys. Rev. E 77, 050901 (2008). [Link to the article]
• Y. Togashi, T. Yanagida,
  BioNanoProcess - Introduction to Wet-Nanotechnology: in aqua Organization of Nano-Structures - (I. Yamashita, K. Shiba, eds.), CMC Publishing, Section 35, 350-358 (2008).
  (in Japanese; 「生物に学ぶナノデバイスの設計思想～ゆらぎの排除から利用へ～」, バイオナノプロセス―溶液中でナノ構造を作るウェット・ナノテクノロジーの勧め―, シーエムシー出版).
• Y. Togashi,
  "Dynamical Features and Design Principles of Protein Machines: Elastic Network Studies",
  (in Japanese; 「タンパク分子機械の力学的特徴と設計原理―弾性ネットワークモデルによる試み」),
  Seibutsu Butsuri (生物物理) 48, 114 (2008). [Link to the article (Free)]
• V. Casagrande, Y. Togashi, A. S. Mikhailov,
  "Molecular Synchronization Waves in Arrays of Allosterically Regulated Enzymes",
  Phys. Rev. Lett. 99, 048301 (2007). [Link to the article] [Preprint (0704.0021)]
• Y. Togashi, A. S. Mikhailov,
  "Nonlinear Relaxation Dynamics in Elastic Networks and Design Principles of Molecular Machines",
  Proc. Natl. Acad. Sci. (USA) 104, 8697-8702 (2007). [Link to the article (Free)] [Preprint (0705.2504)]
• Y. Togashi, K. Kaneko,
  "Switching Dynamics in Reaction Networks Induced by Molecular Discreteness",
  Jour. Phys. Cond. Matt. 19, 065150 (2007). [Link to the article] [Preprint (physics/0612060)]
• Y. Togashi, K. Kaneko,
  "Discreteness-induced Stochastic Steady State in Reaction Diffusion Systems: Self-consistent Analysis and Stochastic Simulations",
  Physica D 205, 87-99 (2005). [Link to the article] [Preprint (physics/0409027)]
• Y. Togashi, K. Kaneko,
  "Discreteness-Induced Transitions in Autocatalytic Systems",
  (unpublished collective work, 2005). [Preprint (physics/0501017)]
• Y. Togashi, K. Kaneko,
  "Molecular Discreteness in Reaction-Diffusion Systems Yields Steady States Not Seen in the Continuum Limit",
  Phys. Rev. E 70, 020901(R) (2004). [Link to the article] [Preprint (physics/0310083)]
• Y. Togashi,
  "Discrete Reaction System - Transition induced by Discreteness of Molecules"
  (in Japanese; 「離散的反応系 ― 分子の離散性がもたらす状態遷移」),
  Ph.D. Thesis, Univ. of Tokyo (2003) (in Japanese). PDF(7.19MB) / Abstract PDF(347kB).
• Y. Togashi, K. Kaneko,
  "Alteration of Chemical Concentrations through Discreteness-Induced Transitions in Small Autocatalytic Systems",
  J. Phys. Soc. Jpn. 72, 62-68 (2003). [Link to the article] [Preprint (physics/0109064)]
• Y. Togashi, K. Kaneko,
  "Transitions Induced by the Discreteness of Molecules in a Small Autocatalytic System",
  Phys. Rev. Lett. 86, 2459-2462 (2001). [Link to the article] [Preprint (physics/0008238)]
• Y. Togashi,
  "Digitality Effect in Reaction Networks"
  (in Japanese; 「反応ネットワークにおける分子数の離散性効果」),
  Master Thesis, Univ. of Tokyo (2001) (in Japanese).
  PS+GZIP(3.95MB) / PDF(8.16MB) / PDF (low resolution)(1.14MB)
  Abstract (in Japanese): 物性研究 76-5, 702 (2001) [Link to the article (Free)].

Information about these publications is also available through ResearcherID.com.

Acknowledgments: These research works were in part supported by Grants-in-Aid for Scientific Research (11CE2006, 15-11161, 20740243, 23115007, 16K05518, 16H01408, 18KK0388, 18H04720, 19H05424, 21K03487), Special Coordination Funds for Promoting Science and Technology (Yuragi Project), and Platform for Dynamic Approaches to Living System from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and Research Fellowships from the Japan Society for the Promotion of Science (15-11161, research abroad H17).
以上の研究は、文部科学省 科研費（特別推進研究(COE)・特別研究員奨励費・若手研究(B)・新学術領域研究・基盤研究(C)・国際共同研究強化(A)）・科学技術振興調整費（先端融合領域イノベーション創出拠点の形成）・研究開発施設共用等促進費補助金（生命動態システム科学推進拠点事業）、並びに、日本学術振興会 特別研究員・海外特別研究員制度の支援を受けて行われました。

Contact:
TOGASHI Yuichi
Ph.D., Professor, Associate Dean
(冨樫 祐一, 立命館大学 生命科学部 生命情報学科 教授・副学部長（入試・高大連携担当）)
Department of Bioinformatics, College of Life Sciences, Ritsumeikan University
1-1-1 Noji-higashi, Kusatsu, Shiga 525-8577, Japan
Tel. +81-77-561-4898 / Fax +81-50-3737-2462
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Also:
Senior Visiting Scientist, Laboratory for Comprehensive Bioimaging, RIKEN Center for Biosystems Dynamics Research (BDR)