Molecular analysis of radiation tolerance in extremotolerant tardigrades

• Project/Area Number: 25281016
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: The University of Tokyo
• Principal Investigator: Kunieda Takekazu 東京大学, 理学(系)研究科(研究院), 助教 (10463879)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2015: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2013: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 放射線耐性 / クマムシ / 緩歩動物 / DNA損傷 / DNA保護 / Dsup / 放射線 / クロマチン / DNA / 保護 / 耐性

Outline of Final Research Achievements

Tardigrades, also known as water bears, are small aquatic animals living in various habitats. They enter an almost completely dehydrated state upon desiccation and exhibit exceptional tolerance against various physical extremes, including direct exposure to space. Here, we identified a novel tardigrade-unique protein named ‘Dsup’ (short for damage suppressor) from a chromatin fraction of a radiation-tolerant tardigrade, Ramazzottius varieornatus. Dsup protein forms a complex with DNA in vitro and is co-localized with nuclear DNA in cells. We engineered human cultured cells to stably express Dsup constitutively, and demonstrated that Dsup-expressing cells exhibited a substantially suppressed occurrence of DNA-breaks after X-ray irradiation and exposure to ROS. Furthermore, survival after X-ray irradiation was significantly improved in Dsup-expressing cells, some of which even retain proliferative ability, though untransfected cells completely cease proliferation.

Research Products

• [Journal Article] Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade-unique protein. (2016)
  • Author(s): Hashimoto T, Horikawa DD, Saito Y, Kuwahara H, Kozuka-Hata H, Shin-I T, Minakuchi Y, Ohishi K, Motoyama A, Aizu T, Enomoto A, Kondo K, Tanaka S, Hara Y, Koshikawa S, Sagara H, Miura T, Yokobori S, Miyagawa K, Suzuki Y, Kubo T, Oyama M, Kohara Y, Fujiyama A, Arakawa K, Katayama T, Toyoda A and Kunieda T
  • Journal Title: Nature Communications Volume: 7 Issue: 1 Pages: 12808-12808
  • DOI: 10.1038/ncomms12808
  • NAID: 120005971035
  • Peer Reviewed / Open Access
• [Journal Article] Novel mitochondria-targeted heat-soluble proteins identified in the anhydrobiotic tardigrade improve osmotic tolerance of human cells. (2015)
  • Author(s): Tanaka, S., Tanaka, J., Miwa Y., Horikawa, D.D., Katayama, T., Arakawa, K., Toyoda, A., Kubo, T., Kunieda, T.
  • Journal Title: PLOS ONE Volume: 10 Issue: 2 Pages: e0118272-e0118272
  • DOI: 10.1371/journal.pone.0118272
  • Peer Reviewed / Open Access
• [Presentation] 極限環境耐性動物クマムシの新規クロマチンタンパク質による哺乳類培養細胞への放射線耐性の付与 (2015)
  • Author(s): 橋本拓磨、斎藤裕樹、尾山大明、秦裕子、榎本敦、宮川清、桑原宏和、堀川大樹、豊田敦、片山俊明、荒川和晴、藤山秋佐夫、久保健雄、國枝武和
  • Organizer: 第67回日本細胞生物学会大会
  • Place of Presentation: 東京都・江戸川
  • Year and Date: 2015-06-30 – 2015-07-02
• [Presentation] 極限環境耐性動物クマムシの新規クロマチンタンパク質による哺乳類培養細胞への放射線耐性の付与 (2015)
  • Author(s): 橋本拓磨、斎藤裕樹、尾山大明、秦裕子、榎本敦、宮川清、桑原宏和、堀川大樹、豊田敦、片山俊明、荒川和晴、藤山秋佐夫、久保健雄、國枝武和
  • Organizer: 第67回日本細胞生物学会大会
  • Place of Presentation: タワーホール船堀（東京都江戸川区）
  • Year and Date: 2015-06-30
• [Presentation] A novel chromatin protein of radiation-resistant animal protects DNA and cells from radiation damages (2015)
  • Author(s): T. Hashimoto, Y. Saito, M. Oyama, H. kozuka-Hata, A. Enomoto, K. Miyagawa, H. Kuwahara, D. D. Horikawa, T. Katayama, K. Arakawa, A. Toyoda, A. Fujiyama, T. Kubo, T. Kunieda
  • Organizer: 13th International Symposium on Tardigrada
  • Place of Presentation: Modena, Italy
  • Year and Date: 2015-06-23 – 2015-06-26
• [Presentation] Comparative Omic Analysis between anhydrobiotic tardigrade and desiccation-sensitive tardigrade (2015)
  • Author(s): Takekazu Kunieda, Makiko Ito, Koyuki Kondo, Sae Tanaka, Takuma Hashimoto, Yohei Minakuchi, Hideki Noguchi, Toshiaki Katayama, Kazuharu Arakawa, Atsushi Toyoda,, Takeo Kubo, Asao Fujiyama
  • Organizer: 13th International Symposium on Tardigrada
  • Place of Presentation: Modena, Italy
  • Year and Date: 2015-06-23 – 2015-06-26
• [Presentation] A novel chromatin protein of radiation-resistant animal protects DNA and cells from radiation damages (2015)
  • Author(s): Hashimoto T, Saito Y, Oyama M, Kozuka-Hata H, Enomoto A, Miyagawa K, Kuwahara H, Horikawa DD, Katayama T, Arakawa K, Toyoda A, Fujiyama A, Kubo T, Kunieda T
  • Organizer: 13th International Symposium on Tardigrada
  • Place of Presentation: Modena (Italy)
  • Year and Date: 2015-06-23
  • Int'l Joint Research
• [Presentation] Comparative omic analysis between anhydrobiotic tardigrade and desiccation-sensitive tardigrade. 13th International symposium on tardigrade (2015)
  • Author(s): Kunieda T, Ito M, Kondo K, Minakuchi Y, Noguchi H, Tanaka S, Hashimoto T, Katayama T, Arakawa K, Toyoda A, Kubo T, Fujiyama A
  • Organizer: 13th International Symposium on Tardigrada
  • Place of Presentation: Modena (Italy)
  • Year and Date: 2015-06-23
  • Int'l Joint Research
• [Presentation] A novel chromatin protein of radiation-resistant animal protects DNA and cells from radiation damages (2015)
  • Author(s): T. Hashimoto, Y. Saito, M. Oyama, H. kozuka-Hata, A. Enomoto, K. Miyagawa, H. Kuwahara, D. D. Horikawa, T. Katayama, K. Arakawa, A. Toyoda, A. Fujiyama, T. Kubo, T. Kunieda.
  • Organizer: 15th International Congress of Radiation Research
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2015-05-25 – 2015-05-29
• [Presentation] A novel chromatin protein of radiation-resistant animal protects DNA and cells from radiation damages. (2015)
  • Author(s): Hashimoto T, Saito Y, Oyama M, Kozuka-Hata H, Enomoto A, Miyagawa K, Kuwahara H, Horikawa DD, Katayama T, Arakawa K, Toyoda A, Fujiyama A, Kubo T, Kunieda T
  • Organizer: 15th International Congress of Radiation Research
  • Place of Presentation: 京都国際会議場（京都府左京区）
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] クマムシにおける乾燥耐性獲得時の遺伝子発現変動解析 (2015)
  • Author(s): 近藤小雪、加藤由起、白髭克彦、久保健雄、國枝武和
  • Organizer: 日本農芸化学会2015年度大会
  • Place of Presentation: 岡山県・岡山
  • Year and Date: 2015-03-29
• [Presentation] 放射線耐性を示すクマムシの新規タンパク質S261によるDNA損傷の抑制 (2014)
  • Author(s): 橋本拓磨、斎藤裕樹、尾山大明、秦裕子、榎本敦、宮川清、桑原宏和、堀川大樹、片山俊明、荒川和晴、豊田敦、藤山秋佐夫、久保健雄、國枝武和
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 神奈川県・横浜
  • Year and Date: 2014-11-27
• [Presentation] 乾燥耐性能力を持たないクマムシのゲノム解読と比較解析 (2014)
  • Author(s): 國枝武和、伊藤麻紀子、近藤小雪、水口洋平、野口英樹、片山俊明、荒川和晴、豊田敦,、久保健雄、藤山秋佐夫
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 神奈川県・横浜
  • Year and Date: 2014-11-27
• [Presentation] ケミカルジェネティクスを用いたクマムシの乾眠に関わるシグナル伝達経路の探索 (2014)
  • Author(s): 近藤 小雪、久保 健雄、國枝 武和
  • Organizer: 日本分子生物学会第37回年会
  • Place of Presentation: 神奈川県・横浜
  • Year and Date: 2014-11-27
• [Presentation] 乾燥耐性動物クマムシで大量発現する新規膜タンパク質A8の解析 (2014)
  • Author(s): 島津拓真、橋本拓磨、阿部耕太、田中冴、片山俊明、荒川和晴、豊田敦、久保健雄、國枝武和
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 神奈川県・横浜
  • Year and Date: 2014-11-25
• [Presentation] 放射線耐性を示すクマムシの新規タンパク質によるDNA損傷の抑制 (2014)
  • Author(s): 橋本拓磨、斎藤裕樹、尾山大明、秦裕子、榎本敦、宮川清、桑原宏和、堀川大樹、片山俊明、荒川和晴、豊田敦、藤山秋佐夫、久保健雄、國枝武和
  • Organizer: 極限環境生物学会2014年度（第15回）年会
  • Place of Presentation: 沖縄県・今帰仁村
  • Year and Date: 2014-11-02
• [Presentation] 乾燥耐性クマムシにおけるミトコンドリア局在タンパク質の同定と解析 (2014)
  • Author(s): 田中冴、秦裕子、尾山大明、豊田敦、片山俊明、荒川和晴、藤山秋佐夫、久保健雄、國枝武和
  • Organizer: 第15回極限環境生物学会
  • Place of Presentation: 沖縄県・今帰仁村
  • Year and Date: 2014-11-01 – 2014-11-03
• [Presentation] 放射線耐性を示すクマムシの新規タンパク質S261によるDNA損傷の抑制 (2014)
  • Author(s): 橋本拓磨、斎藤裕樹、尾山大明、秦裕子、榎本敦、宮川清、桑原宏和、堀川大樹、豊田敦、片山俊明、荒川和晴、藤山秋佐夫、久保健雄、國枝武和
  • Organizer: 日本放射線影響学会第57回大会
  • Place of Presentation: 鹿児島県・鹿児島
  • Year and Date: 2014-10-02
• [Presentation] 放射線耐性を示すクマムシの新規タンパク質によるDNA損傷の抑制 (2014)
  • Author(s): 橋本拓磨、斎藤裕樹、尾山大明、秦裕子、榎本敦、宮川清、桑原宏和、堀川大樹、豊田敦、藤山秋佐夫、久保健雄、國枝武和
  • Organizer: 日本動物学会第85回大会
  • Place of Presentation: 宮城県・仙台
  • Year and Date: 2014-09-13
• [Presentation] クマムシにおけるミトコンドリアの乾燥耐性機構の分子基盤解析 (2014)
  • Author(s): 田中冴、秦裕子、尾山大明、豊田敦、片山俊明、荒川和晴、藤山秋佐夫、久保健雄、國枝武和
  • Organizer: 第３回マトリョーシカ型生物学研究会若手招待講演
  • Place of Presentation: 兵庫県・神戸市
  • Year and Date: 2014-07-11 – 2014-07-13
  • Invited
• [Presentation] クマムシの耐性の秘密を探る (2014)
  • Author(s): 國枝武和
  • Organizer: 第37回日本土壌動物学会大会
  • Place of Presentation: 埼玉県飯能市
  • Year and Date: 2014-05-24
  • Invited
• [Presentation] 高い放射線耐性を示すヨコヅナクマムシの新規クロマチンタンパク質S261の解析 (2014)
  • Author(s): 橋本拓磨、斎藤裕樹、尾山大明、秦裕子、桑原宏和、堀川大樹、豊田敦、片山俊明、荒川和晴、藤山秋佐夫、久保健雄、國枝武和
  • Organizer: 第十四回 東京大学 生命科学シンポジウム
  • Place of Presentation: 東京都・文京
  • Year and Date: 2014-04-26
• [Presentation] 高い放射線耐性を示すヨコヅナクマムシの新規クロマチンタンパク質S261の解析 (2014)
  • Author(s): 橋本拓磨、斎藤裕樹、尾山大明、秦裕子、桑原宏和、堀川大樹、豊田敦、片山俊明、荒川和晴、藤山秋佐夫、久保健雄、國枝武和
  • Organizer: 日本動物学会関東支部第66回大会
  • Place of Presentation: 千葉県・柏
• [Presentation] 高い放射線耐性を示すクマムシの新規クロマチンタンパク質の解析 (2013)
  • Author(s): 橋本拓磨、斎藤裕樹、尾山大明、秦裕子、桑原宏和、堀川大樹、豊田敦、片山俊明、荒川和晴、藤山秋佐夫、久保健雄、國枝武和
  • Organizer: 日本動物学会第84回大会
  • Place of Presentation: 岡山県・岡山
• [Presentation] ヨコヅナクマムシの新規クロマチンタンパク質S261によるDNA 断片化の抑制 (2013)
  • Author(s): 橋本拓磨、斎藤裕樹、尾山大明、秦裕子、桑原宏和、堀川大樹、豊田敦、片山俊明、荒川和晴、藤山秋佐夫、久保健雄、國枝武和
  • Organizer: 極限環境生物学会第14回年会
  • Place of Presentation: 神奈川県・川崎
• [Presentation] 高い放射線耐性を示すヨコヅナクマムシの新規クロマチンタンパク質S261の解析 (2013)
  • Author(s): 橋本拓磨、斎藤裕樹、尾山大明、秦裕子、桑原宏和、堀川大樹、豊田敦、片山俊明、荒川和晴、藤山秋佐夫、久保健雄、國枝武和
  • Organizer: 日本放射線影響学会第56回大会
  • Place of Presentation: 青森県・青森
• [Presentation] 高い放射線耐性を示すヨコヅナクマムシの新規クロマチンタンパク質S261の解析 (2013)
  • Author(s): 橋本拓磨、斎藤裕樹、尾山大明、秦裕子、桑原宏和、堀川大樹、豊田敦、片山俊明、荒川和晴、藤山秋佐夫、久保健雄、國枝武和
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 兵庫県・神戸
• [Presentation] Proteomic analysis of chromatin fraction in an anhydrobiotic tardigrade, Ramazzottius varieornatus (2013)
  • Author(s): T. Hashimoto, Y. Saito, M. Oyama, H. Kozuka-Hata, H. Kuwahara, D. D. Horikawa, A. Toyoda, T. Katayama, K. Arakawa, A. Fujiyama, T. Kubo, T. Kunieda
  • Organizer: 29th RBC-NIRS International Symposium
  • Place of Presentation: 京都府・京都
• [Book] 極限環境生命―生命の起源を考え、その多様性に学ぶ (2014)
  • Author(s): 伊藤 政博, 鳴海 一成, 佐藤 孝子, 中村 聡, 東端 啓貴, 國技 武和, 為我井 秀行, 道久 則之, 伊藤 隆
  • Total Pages: 220
  • Publisher: コロナ社
• [Remarks] くまむし研究グループ
  • URL: http://www.biol.s.u-tokyo.ac.jp/users/saibou/kuma/
• [Remarks] ヒト培養細胞の放射線耐性を向上させる新規タンパク質をクマムシのゲノムから発見
  • URL: https://www.s.u-tokyo.ac.jp/ja/press/2016/5001/
• [Patent(Industrial Property Rights)] DNA傷害抑制剤 (2015)
  • Inventor(s): 國枝武和、橋本拓磨
  • Industrial Property Rights Holder: 國枝武和、橋本拓磨
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-032209
  • Filing Date: 2015-02-20