Biological and medical approach to cellular function based on intracellular thermometry

• Project/Area Number: 17H03075
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Analytical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: UCHIYAMA SEIICHI 東京大学, 大学院薬学系研究科(薬学部), 助教 (10401225)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2020: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2017: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
• Keywords: 蛍光 / 細胞 / 温度 / 分析 / イメージング

Outline of Final Research Achievements

We have synthesized the first cationic radical initiator (ADIP) and prepared non-toxic cationic fluorescent nanogel thermometers. By using the new nanogel thermometers, long-term monitoring of intracellular temperature can be performed. In addition, the effects of maturation of brown adipocytes on their thermogenesis were investigated. The contribution of pannexin-1 on the thermogenesis was also elucidated.

Academic Significance and Societal Importance of the Research Achievements

研究代表者は、世界で初めて蛍光性温度センサーを用いて、生きた細胞の温度計測を行った本分野の先駆者である。本課題の成果は、細胞内温度計測における蛍光性温度センサーの有用性を確固たるものにした他、生物学的・医学的にも興味を持たれている褐色脂肪細胞の熱産生メカニズムに迫ったものである。本成果を通じて、生物学や医学において細胞内温度計測技術が非常に有効であることを示すと同時に、幅広い分野の研究者に本法の重要性を伝えることができた。

Research Products

• [Int'l Joint Research] University of Virginia(米国)
• [Int'l Joint Research] University of Technology Sydney(オーストラリア)
• [Int'l Joint Research] Universidad Autonoma de Madrid(スペイン)
• [Int'l Joint Research] Queen’s University(英国)
• [Int'l Joint Research] UMR PAM(フランス)
• [Int'l Joint Research] Univ. of Virginia School of Medicine(米国)
• [Int'l Joint Research] University of Ulm(ドイツ)
• [Journal Article] Intracellular thermometry uncovers spontaneous thermogenesis and associated thermal signaling (2021)
  • Author(s): Kohki Okabe, Seiichi Uchiyama
  • Journal Title: Communications Biology Volume: 4 Issue: 1 Pages: 1377-1377
  • DOI: 10.1038/s42003-021-02908-2
  • Peer Reviewed / Open Access
• [Journal Article] Adaptive thermogenesis in brown adipose tissue involves activation of pannexin-1 channels (2021)
  • Author(s): Subramanian Senthivinayagam et al.
  • Journal Title: Molecular Metabolism Volume: 44 Pages: 101130-101130
  • DOI: 10.1016/j.molmet.2020.101130
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Advances and challenges for fluorescence nanothermometry (2020)
  • Author(s): Jiajia Zhou, Blanca del Rosal, Daniel Jaque, Seiichi Uchiyama, Dayong Jin
  • Journal Title: Nature Methods Volume: 17 Issue: 10 Pages: 967-980
  • DOI: 10.1038/s41592-020-0957-y
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The Magical Combination of Polymer Science and Fluorometry (2020)
  • Author(s): Seiichi Uchiyama
  • Journal Title: Polymers Volume: 12 Issue: 4 Pages: 876-876
  • DOI: 10.3390/polym12040876
  • Open Access
• [Journal Article] Fluorescent Sensors Based on a Novel Functional Design: Combination of an Environment-sensitive Fluorophore with Polymeric and Self-assembled Architectures (2019)
  • Author(s): Seiichi Uchiyama
  • Journal Title: Journal of Synthetic Organic Chemistry, Japan Volume: 77 Issue: 11 Pages: 1116-1127
  • DOI: 10.5059/yukigoseikyokaishi.77.1116
  • NAID: 130007742537
  • ISSN: 0037-9980, 1883-6526
  • Year and Date: 2019-11-01
  • Peer Reviewed / Open Access
• [Journal Article] Cationic Fluorescent Nanogel Thermometers based on Thermoresponsive Poly(N-isopropylacrylamide) and Environment-Sensitive Benzofurazan (2019)
  • Author(s): Teruyuki Hayashi, Kyoko Kawamoto, Noriko Inada, Seiichi Uchiyama
  • Journal Title: Polymers Volume: 11 Issue: 8 Pages: 1305-1305
  • DOI: 10.3390/polym11081305
  • Peer Reviewed / Open Access
• [Journal Article] A Personal Journey across Fluorescent Sensing and Logic Associated with Polymers of Various Kinds (2019)
  • Author(s): Chao-Yi Yao, Seiichi Uchiyama, A. Prasanna de Silva
  • Journal Title: Polymers Volume: 11 Issue: 8 Pages: 1351-1351
  • DOI: 10.3390/polym11081351
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 薬学におけるナノゲル研究の最前線 (2019)
  • Author(s): 内山聖一、徳山英利
  • Journal Title: Farumashia Volume: 55 Issue: 8 Pages: 770-774
  • DOI: 10.14894/faruawpsj.55.8_770
  • NAID: 130007686651
  • ISSN: 0014-8601, 2189-7026
• [Journal Article] Temperature imaging using a cationic linear fluorescent polymeric thermometer and fluorescence lifetime imaging microscopy (2019)
  • Author(s): Noriko Inada, Nanaho Fukuda, Teruyuki Hayashi, Seiichi Uchiyama
  • Journal Title: Nature Protocols Volume: 14 Issue: 4 Pages: 1293-1321
  • DOI: 10.1038/s41596-019-0145-7
  • Peer Reviewed
• [Journal Article] A Cell-Targeted Non-Cytotoxic Fluorescent Nanogel Thermometer Created with an Imidazolium-Containing Cationic Radical Initiator. (2018)
  • Author(s): Uchiyama, S., Tsuji, T., Kawamoto, K., Okano, K., Fukatsu, E., Noro, T., Ikado, K., Yamada, S., Shibata, Y., Hayashi, T., Inada, N., Kato, M., Koizumi, H., and Tokuyama, H.
  • Journal Title: Angewandte Chemie Volume: 57 Issue: 19 Pages: 5413-5417
  • DOI: 10.1002/anie.201801495
  • Peer Reviewed / Open Access
• [Journal Article] アゾ系カチオン性ラジカル重合開始剤の開発 (2018)
  • Author(s): 内山聖一、徳山英利
  • Journal Title: 化学 Volume: 73(12) Pages: 47-52
• [Journal Article] Intracellular temperature measurements with fluorescent polymeric thermometers. (2017)
  • Author(s): Uchiyama, S., Gota, C., Tsuji, T., and Inada, N.
  • Journal Title: Chemical Communications Volume: 53 Issue: 80 Pages: 10976-10992
  • DOI: 10.1039/c7cc06203f
  • Peer Reviewed / Open Access
• [Journal Article] Difference in intracellular temperature rise between matured and precursor brown adipocytes in response to uncoupler and β-adrenergic agonist stimuli (2017)
  • Author(s): Toshikazu Tsuji, Kumiko Ikado, Hideki Koizumi, Seiichi Uchiyama, Kazuaki Kajimoto
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 12889-12889
  • DOI: 10.1038/s41598-017-12634-7
  • Peer Reviewed / Open Access
• [Journal Article] 蛍光温度プローブと蛍光寿命測定による細胞内温度イメージング (2017)
  • Author(s): 稲田のりこ、内山聖一
  • Journal Title: 光アライアンス Volume: 28(8) Pages: 33-37
• [Presentation] Fluorescent polymeric thermometers for intracellular thermometry (2020)
  • Author(s): Seiichi Uchiyama
  • Organizer: Three Wise Men Winter School on Luminescent Nanothermometry for Biomedical Applications
  • Int'l Joint Research / Invited
• [Presentation] Intracellular Temperature Measurements with Fluorescent Polymeric Thermometers (2019)
  • Author(s): Seiichi Uchiyama
  • Organizer: 7th Annual Conference of AnalytiX-2019
  • Int'l Joint Research / Invited
• [Presentation] Intracellular thermometry with fluorescent polymeric thermometers (2019)
  • Author(s): Seiichi Uchiyama
  • Organizer: Interphotonics 2019
  • Int'l Joint Research / Invited
• [Presentation] 細胞内温度計測の歴史とこれから (2019)
  • Author(s): 内山聖一
  • Organizer: 計測自動制御学会 第149回温度計測部会講演会
  • Invited
• [Presentation] レシオ型蛍光性温度センサーによる褐色脂肪細胞の温度計測 (2018)
  • Author(s): 内山聖一、辻俊一、井門久美子、河本恭子、稲田のりこ
  • Organizer: 第78回分析化学討論会
• [Presentation] Intracellular temperature measurements with fluorescent polymeric thermometers (2018)
  • Author(s): Seiichi Uchiyama
  • Organizer: 6th International Conference on Molecular Sensors and Molecular Logic Gates (MSMLG2018)
  • Int'l Joint Research / Invited
• [Presentation] A cationic fluorescent polymeric thermometer for the ratiometric sensing of intracellular temperature (2018)
  • Author(s): Seiichi Uchiyama, Toshikazu Tsuji, Kumiko Ikado, Aruto Yoshida, Kyoko Kawamoto, Teruyuki Hayashi, Noriko Inada
  • Organizer: World Polymer Congress Macro2018
  • Int'l Joint Research
• [Presentation] Ratiometric sensing of intracellular temperature with a cationic fluorescent polymeric thermometer (2018)
  • Author(s): Seiichi Uchiyama, Toshikazu Tsuji, Kumiko Ikado, Aruto Yoshida, Kyoko Kawamoto, Teruyuki Hayashi, Noriko Inada
  • Organizer: 27th PhotoIUPAC 2018 (International Symposium on Photochemistry)
  • Int'l Joint Research
• [Presentation] 新規イミダゾリウム系カチオン性ラジカル重合開始剤による細胞内移行性のある無毒性蛍光ナノゲル温度計の開発 (2018)
  • Author(s): 辻俊一、内山聖一、小泉英樹、井門久美子、山田小百合、稲田のりこ、徳山英利
  • Organizer: 第27回ポリマー材料フォーラム
• [Presentation] An environment-sensitive fluorophore methoxybenzocoumarin emitting in protic environments (2017)
  • Author(s): Seiichi Uchiyama, Kyoko Kawamoto, Chie Gota, Toshitada Yoshihara, Seiji Tobita, Patricia Remon, Uwe Pischel
  • Organizer: 28th International Conference on Photochemistry (ICP2017)
  • Int'l Joint Research
• [Presentation] 細胞内温度測定による褐色脂肪細胞の直接的な熱産生測定手法の構築 (2017)
  • Author(s): 辻俊一、内山聖一、梶本和昭
  • Organizer: 第38回日本肥満学会
• [Presentation] 感温性高分子による生細胞の温度測定 (2017)
  • Author(s): 内山聖一
  • Organizer: 金沢大学薬学シンポジウム2017 「イメージング研究が切り開く生命科学の最前線」
  • Invited