Non-contact and non-invasive manipulation of biological functionalities using all-optical method

• Project/Area Number: 17H06228
• Research Category: Grant-in-Aid for Challenging Research (Pioneering)
• Allocation Type: Single-year Grants
• Research Field: Applied physics and engineering and related fields
• Research Institution: Kyoto University
• Principal Investigator: Hirori Hideki 京都大学, 化学研究所, 准教授 (00512469)
• Co-Investigator(Kenkyū-buntansha): 坂口 怜子 京都大学, 工学研究科, 助教 (80723197)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000); Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
• Keywords: 高強度テラヘルツ / 非線形分光 / ライブセルイメージング / 蛍光プローブ / 分化誘導 / 細胞機能制御 / 再生医療 / iPS細胞 / 非線形光学 / 高強度THz / 細胞制御 / 生体機能制御

Outline of Final Research Achievements

We establish a setup utilized for studying the effects of THz light irradiation on human induced pluripotent stem cells (hiPSCs). By utilizing a microfabricated micro-well dish for culturing hiPSCs, we are able to continuously irradiate THz light on hiPSCs without their abnormal morphological changes. RNA sequencing for global gene expression analysis reveals that many of THz-regulated genes are transcription factors of zinc finger proteins (ZFNs). These results imply that THz radiation results the intracellular concentration changes of metallic ions, such as Zn2+.

Academic Significance and Societal Importance of the Research Achievements

これまでにテラヘルツ光パルスが、生細胞の非侵襲的操作の生物医学的応用に利用されています。本研究では、環境に敏感な人工多能性幹細胞（hiPSC）に高強度な電場パルスであるテラヘルツ光パルス励起を適用し、亜鉛フィンガー（ZNF）転写因子に関連する遺伝子発現ネットワークを操作できることを発見しました。 ここで構築したテラヘルツ光パルス照射装置による非侵襲的な細胞操作方法は、基本的な幹細胞研究と生物医学的アプリケーションの両方に向けた、細胞の電磁制御の新しいアプローチになることを示しました。

Research Products

• [Int'l Joint Research] Rush University Medical Center(米国)
• [Int'l Joint Research] Universiti Pendidikan Sultan Idris(マレーシア)
• [Journal Article] Contribution of Coiled-Coil Assembly to Ca2+/Calmodulin-Dependent Inactivation of TRPC6 Channel and its Impacts on FSGS-Associated Phenotypes (2019)
  • Author(s): Polat Onur K.、Uno Masatoshi、Maruyama Terukazu、Tran Ha Nam、Imamura Kayo、Wong Chee Fah、Sakaguchi Reiko、Ariyoshi Mariko、Itsuki Kyohei、Ichikawa Jun、Morii Takashi、Shirakawa Masahiro、Inoue Ryuji、Asanuma Katsuhiko、Reiser Jochen、Tochio Hidehito、Mori Yasuo、Mori Masayuki X.
  • Journal Title: Journal of the American Society of Nephrology Volume: 30 Issue: 9 Pages: 1587-1603
  • DOI: 10.1681/asn.2018070756
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] TRPM7 channels mediate spontaneous Ca2+ fluctuations in growth plate chondrocytes that promote bone development. (2019)
  • Author(s): Qian N, Ichimura A, Takei D, Sakaguchi R, Kitani A, Nagaoka R, Tomizawa M, Miyazaki Y, Miyachi H, Numata T, Kakizawa S, Nishi M, Mori Y, Takeshima H.
  • Journal Title: Science signaling Volume: 12 Issue: 576 Pages: 4847-4847
  • DOI: 10.1126/scisignal.aaw4847
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ultrafast reflectivity change of vanadium dioxide induced by THz field enhanced by a metallic structure (2019)
  • Author(s): Tachizaki Takehiro、Hattori Azusa N.、Tanaka Hidekazu、Hirori Hideki
  • Journal Title: Japanese Journal of Applied Physics Volume: 58 Issue: 8 Pages: 083002-083002
  • DOI: 10.7567/1347-4065/ab2e97
  • Peer Reviewed
• [Journal Article] Zener tunneling breakdown in phase-change materials revealed by intense terahertz pulses (2018)
  • Author(s): Yasuyuki Sanari, Takehiro Tachizaki, Yuta Saito, Kotaro Makino, Paul Fons, Alexander V. Kolobov, Junji Tominaga, Koichiro Tanaka, Yoshihiko Kanemitsu, Muneaki Hase, and Hideki Hirori
  • Journal Title: Phys. Rev. Lett. Volume: 121 Issue: 16 Pages: 165702-165702
  • DOI: 10.1103/physrevlett.121.165702
  • NAID: 120006532091
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Coherent detection of THz-induced sideband emission from excitons in the nonperturbative regime (2018)
  • Author(s): K. Uchida, T. Otobe, T. Mochizuki, C. Kim, M. Yoshita, K. Tanaka, H. Akiyama, L. N. Pfeiffer, K. W. West, and H. Hirori
  • Journal Title: PHYSICAL REVIEW B Volume: 97 Issue: 16 Pages: 165122-165122
  • DOI: 10.1103/physrevb.97.165122
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 蛍光性タンパク質温度センサーを用いた生体内温度分布の可視化とその意義の解明 (2019)
  • Author(s): 坂口 怜子, 森 泰生
  • Organizer: 第19回日本蛋白質科学会年会 第71回日本細胞生物学会大会 合同年次大会
  • Invited
• [Presentation] Development of fluorescent tools to visualize intracellular signaling (2019)
  • Author(s): Reiko Sakaguchi
  • Organizer: International Symposium of Biofunctional Chemistry
  • Invited
• [Presentation] Development of Intracellular Thermosensors for the Understanding of Energy Production in Mitochondria (2018)
  • Author(s): Reiko Sakaguchi
  • Organizer: The 9th International Symposium of Advanced Energy Science, (Kihada Hall, Uji Obaku Plaza, Kyoto University)
  • Int'l Joint Research / Invited
• [Presentation] 二光子励起リン光寿命イメージングによる腫瘍深部酸素濃度の非侵襲的定量 (2018)
  • Author(s): 坂口怜子, et al.
  • Organizer: 第41回日本分子生物学会年会（パシフィコ横浜）
• [Presentation] Non-invasive, quantitative visualization of oxygen environment deep inside tumor spheroids by 2-photon excitation phosphorescence lifetime imaging. (2017)
  • Author(s): Reiko Sakaguchi, Seiji Tobita, Yasuo Mori
  • Organizer: 第5回低酸素研究会
• [Remarks] 高強度テラヘルツパルスによる相変化材料の新たな結晶成長機構の発見
  • URL: http://www.kyoto-u.ac.jp/ja/research/research_results/2018/181019_1.html