宇宙からひも解く新たな生命制御機構の統合的理解

• Project Area: "LIVING IN SPACE" - Integral Understanding of life-regulation mechanism from "SPACE"
• Project/Area Number: 15K21745
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Multi-year Fund
• Review Section: Complex systems
• Research Institution: Japan Aerospace EXploration Agency
• Principal Investigator: 古川 聡 国立研究開発法人宇宙航空研究開発機構, 有人宇宙技術部門, 上席研究開発員 (20726260)
• Project Period (FY): 2015-11-06 – 2020-03-31
• Project Status: Granted (Fiscal Year 2017)
• Budget Amount: ¥74,100,000 (Direct Cost: ¥57,000,000、Indirect Cost: ¥17,100,000); Fiscal Year 2019: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000); Fiscal Year 2018: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000); Fiscal Year 2017: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000); Fiscal Year 2016: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000); Fiscal Year 2015: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000)
• Keywords: 宇宙 / 無重力 / ストレス / 放射線 / 微生物

Outline of Annual Research Achievements

H29年度は研究代表者枠派遣1件、若手研究者派遣8件、海外研究者招聘5件、海外若手研究者招聘11件を実施した。H29年度は本基金による国際共同研究で3本の論文publishがなされた。更に国際共同研究が始まっている。また、同時に若手交流促進や人材育成に貢献している。
[A01]宇宙からひも解かれる生命分子基盤の理解を達成目標に、重力はじめ力学的ストレスに対する細胞、神経―筋の細胞間、筋や腱組織のメカノセンシング機構から適応応答、発達制御、長期無重力や加齢による萎縮・破綻に至る仕組みについて、バイオイメージングやトランスクリプトーム、プロテオーム等先端手法を用いて解析を進めている。
[A02]生命体が個体として有する高次恒常性・適応機構と生命医学への展開として、重力と閉鎖環境に対する循環系、前庭系、精神・自律神経系、睡眠・覚醒、統合的理解を、ヒトを主な研究対象とし、生理・生化学的データ、遺伝子発現、エピゲノム解析、さらにはメンタルストレスに対する新たな客観的評価分析法を開発するなど、基礎医学的解析を中心に実施している。
[A03]宇宙環境によるリスク因子研究とその克服として、宇宙放射線の中でも特に単位面積当たりとして少ないが、高いエネルギーを付与する重粒子放射線、重力変化と宇宙放射線の複合作用、太陽紫外線を含む様々な宇宙放射線、無重力に伴うバイオフィルム形成や遺伝子伝播を含めた微生物間相互作用への影響について評価・分析し、リスク対策方法の開発を展開している。
領域課題の横断・補完的研究[B01]で、放射線被ばくによる細胞ダメージ可視化等を行っている。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

国際活動支援班基金開始から3年経ち、H29年度は本基金による国際共同研究で3本の論文publishがなされた。また、H29年度は外国への研究者派遣や、外国からの研究者招聘件数が前年度より増加し、それに伴い多くの国際共同研究が始まっている。単純割りだとやや遅れ気味なレベルまで取り戻している。
以上の理由により、現状おおむね順調に進展していると考える。

Strategy for Future Research Activity

新たに選定された公募班研究者や関連若手研究者を対象に、H30年度も多くの研究者を派遣や招聘予定で、多くの国際共同研究が期待される。現時点で既にH30年度として330万円程度がほぼ確定しており、基金を有効活用できる見込みである。

Research Products

• [Int'l Joint Research] スタンフォード大学/ハーバード大学/バージニア大学(アメリカ合衆国)
• [Int'l Joint Research] ドイツ航空宇宙センター/マールブルグ大学/Institute of Aerospace Medicine(ドイツ)
• [Int'l Joint Research] パスツール研究所(フランス)
• [Int'l Joint Research] Institute of Science and Technology(オーストリア)
• [Int'l Joint Research] スウェーデン農業科学大学(スウェーデン)
• [Int'l Joint Research] スタンフォード大学/フロリダ州立大学/バージニア大学(アメリカ合衆国)
• [Int'l Joint Research] German Aerospace Center/マールブルグ大学/Institute of Aerospace Medicine(ドイツ )
• [Int'l Joint Research] パスツール研究所(フランス)
• [Int'l Joint Research] Institute of Science and Technology(オーストリア)
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  • Author(s): Oishi Yo、Xu Qi、Wang Lu、Zhang Bin-Jia、Takahashi Koji、Takata Yohko、Luo Yan-Jia、Cherasse Yoan、Schiffmann Serge N.、de Kerchove d’Exaerde Alban、Urade Yoshihiro、Qu Wei-Min、Huang Zhi-Li、Lazarus Michael
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  • Journal Title: npj Microgravity Volume: 2 Pages: 15022-15022
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  • Author(s): Ogawa Y, Yanagida R, Ueda K, Aoki K, Iwasaki K
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  • Author(s): Takase K, Tsuneoka Y, Oda S, Kuroda M, Funato H
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• [Journal Article] Comprehensive analysis of the skin fungal microbiota of astronauts during a half-year stay at the International Space Station (2016)
  • Author(s): Sugita T, Yamazaki T, Makimura K, Cho O, Yamada S, Ohshima H, Mukai C
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  • Author(s): Ahmadi B, Mirhendi H, Makimura K, de Hoog GS, Shidfar MR, Nouripour-Sisakht S, Jalalizand N
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• [Journal Article] Fatal Cyberlindnera fabianii fungemia in a patient with mixed phenotype acute leukemia after umbilical cord blood transplantation (2016)
  • Author(s): Katagiri S, Gotoh M, Tone K, Akahane D, Ito Y, Ohyashiki K, Makimura K
  • Journal Title: Int J Hematol Volume: published online
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  • Peer Reviewed
• [Journal Article] Epidemiological aspects of Dermatophytosis in Khusestan, southwestern Iran, an update (2016)
  • Author(s): Razaei-Matehkolaei A, Rafiei A, Makimura K, Graser Y, Gharghani M, Sadeghi-Nejad B
  • Journal Title: Mycopathologia Volume: published online
  • DOI: 10.1007/s11046-016-9990-x
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Mest but not miR-335 affects skeletal muscle growth and regeneration (2015)
  • Author(s): Hiramuki Y, Sato T, Furuta Y, Surani A, Sehara-Fujisawa A
  • Journal Title: PLoS One Volume: 10
  • DOI: 10.1371/journal.pone.0130436
  • NAID: 120005756262
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• [Journal Article] High-resolution live imaging reveals axon-glia interactions during peripheral nerve injury and repair (2015)
  • Author(s): Xiao Y, Faucherre A, Pola-Morell L, Heddleston J, Liu T, Chew T, Sato F, Sehara-Fujisawa A, Kawakami K, Lopez-Schier H
  • Journal Title: Disease Models & Mechanisms Volume: 8 Pages: 553-564
  • DOI: 10.1242/dmm.018184
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• [Journal Article] Early pathogenesis of Duchenne muscular dystrophy modelled in patient-derived human induced pluripotent stem cells. (2015)
  • Author(s): Shoji E, Sakurai H, Nishino T, Nakahata T, Heike T, Awaya T, Fujii N, Manabe Y, Matsuo M, Sehara-Fujisawa A
  • Journal Title: Scientific Reports. Volume: 5 Pages: 12831-12831
  • DOI: 10.1038/srep12831
  • NAID: 120005649326
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Molecular dynamics study on protein–water interplay in the mechanogating of the bacterial mechanosensitive channel MscL (2015)
  • Author(s): Sawada Y, Sokabe M
  • Journal Title: Eur J Biophys Volume: 44 Pages: 531-43
  • DOI: 10.1007/s00249-015-1065-2
  • Peer Reviewed / Open Access
• [Journal Article] Unidirectional incorporation of a bacterial mechanosensitive channel into liposomal membranes (2015)
  • Author(s): Nomura T, Cox CD, Bavi N, Sokabe M and Martinac B
  • Journal Title: FASEB J Volume: 29 Pages: 4334-4345
  • DOI: 10.1096/fj.15-275198
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Ion Channels Activated by Mechanical Forces in Bacterial and Eukaryotic Cells (2015)
  • Author(s): Sokabe M, Sawada M, Kobayashi T
  • Journal Title: Subcell Biochem: high Pressure Bioscience-Basic Concepts, Applications and Frontiers Volume: 72 Pages: 613-26
  • DOI: 10.1007/978-94-017-9918-8_28
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Hypergravity Provokes a Temporary Reduction in CD4+CD8+ Thymocyte Number and a Persistent Decrease in Medullary Thymic Epithelial Cell Frequency in Mice. (2015)
  • Author(s): Tateishi R, Akiyama N, Miyauchi M, Yoshinaga R, Sasanuma H, Kudo T, Shimbo M, Shinohara M, Obata K, Inoue J, Shirakawa M, Shiba D, Asahara H, Yoshida N, Takahashi S, Morita H, Akiyama T
  • Journal Title: PLoS One Volume: 10 Pages: 1-17
  • DOI: 10.1371/journal.pone.0141650
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Feasibility of a Short-Arm Centrifuge for Mouse Hypergravity Experiments. (2015)
  • Author(s): Morita H, et al.
  • Journal Title: PLoS One Volume: 10(7): e133981 Pages: 1-14
  • DOI: 10.1371/journal.pone.0133981
  • NAID: 120005656590
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of osteoclasis in the heterotopic ossification enhanced by fobrodysplasia ossificans progressiva-related activin-like kinase 2 mutation in mice (2015)
  • Author(s): Kawao N, Yano M, Tamura Y, Okumoto K, Okada K, Kaji H
  • Journal Title: J Bone Miner Metab Volume: epub
  • Peer Reviewed
• [Journal Article] Clinical charasteristics of patients with abnornal ocular/cervical vestibular evoked myogenic potentials in the presence of normal caloric responses (2015)
  • Author(s): Iwasaki S, Fujimoto C, Kinoshita M, Kamogashira T, Egami N, Yamasoba T
  • Journal Title: Ann Otol Rhinol Laryngol Volume: 124 Pages: 458-65
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• [Journal Article] The effect of aging on the center-of-pressure power spectrum in foam posturography (2015)
  • Author(s): Fujimoto C, Egami N, Demura S, Yamasoba T, Iwasaki S.
  • Journal Title: Neuroscience letters Volume: 585 Pages: 92-7
  • DOI: 10.1016/j.neulet.2014.11.033
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Transformation of naltrexone into mesembrane and investigation of the binding properties of its intermediate derivatives to opioid receptors (2015)
  • Author(s): Konoura K, Fujii H, Imaide S, Gouda H, Hirayama S, Hirono S, Nagase H
  • Journal Title: Bioorg. Med. Chem. Volume: 23 Pages: 439-448
  • DOI: 10.1016/j.bmc.2014.12.032
  • NAID: 120005555623
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Peripheral opioid antagonist enhances the effect of anti-tumor drug by blocking a cell growth-suppressive pathway in vivo. (2015)
  • Author(s): Masami Suzuki, Fumiko Chiwaki, Yumi Sawada, Maho Ashikawa, Kazuhiko Aoyagi, Takeshi Fujita, Kazuyoshi Yanagihara, Masayuki Komatsu, Minoru Narita, Tsutomu Suzuki, Hiroshi Nagase, Ryoji Kushima, Hiromi Sakamoto, Takeo Fukagawa, Hitoshi Katai, Hitoshi Nakagama, Teruhiko Yoshida, Yasuhito Uezono, Hiroki Sasaki
  • Journal Title: PLoS One. Volume: 10(4) Pages: 1-18
  • DOI: 10.1371/journal.pone.0123407
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• [Journal Article] Naltrindole derivatives with fluorinated ethyl substituents on 17-nitrogen as delta opioid receptor inverse agonist (2015)
  • Author(s): Nemoto T, Iihara Y, Hirayama S, Iwai T, Higashi E, Fujii H, Nagase H
  • Journal Title: Bioorg Med Chem Lett Volume: 25 Pages: 2927-30
  • DOI: 10.1016/j.bmcl.2015.05.038
  • Peer Reviewed
• [Journal Article] Naltrindole derivatives with fluorinated ethyl substituents on 17-nitrogen as δ opioid receptor inverse agonist (2015)
  • Author(s): Kutsumura, N.; Nakajima, R.; Koyama, Y.; Miyata, Y.; Saitoh, T.; Yamamoto, N.; Iwata, S.; Fujii, H.; Nagase, H.
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• [Journal Article] Inhibition of opioid systems in the hypothalamus as well as the mesolimbic area suppresses feeding behavior of mice (2015)
  • Author(s): Ikeda H, Ardianto C, Yonemochi N, Yang L, Ohashi T, Ikegami M, Nagase H, Kamei J
  • Journal Title: NeuroScience Volume: 311 Pages: 9-21
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• [Journal Article] Design and synthesis of non-peptide, selective orexin receptor 2 agonists (2015)
  • Author(s): Nagahara T, Saitoh T, Kutsumura N, Irukayama-Tomobe Y, Ogawa Y, Kuroda D, Gouda H, Kumagai H, Fujii H, Yanagisawa M, Nagase H
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• [Journal Article] Synthesis of new opioid derivatives with a propellane skeleton and their pharmacologies: Part 5, novel pentacyclic propellane derivatives with a 6-amide side chain (2015)
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• [Journal Article] Endothelin-1 as a master regulator of whole-body Na+ homeostasis (2015)
  • Author(s): Speed JS, Heimlich JB, Hyndman KA, Fox BM, Patel V, Yanagisawa M, Pollock JS, Titze JM, Pollock DM
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• [Journal Article] Functional ETA-ETB receptor cross-talk in basilar artery in situ from ETB receptor deficient rats (2015)
  • Author(s): Yoon S, Gariepy CE, Yanagisawa M, Zuccarello M, Rapoport RM
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• [Journal Article] 長期宇宙滞在時に解決すべき医学的課題～循環制御関連を中心に～ (2015)
  • Author(s): 古川聡
  • Journal Title: 循環制御 Volume: 36 Pages: 66-8
  • Open Access
• [Journal Article] UV-B-Induced CPD Photolyase Gene Expression is Regulated by UVR8-Dependent and -Independent Pathways in Arabidopsis (2015)
  • Author(s): Li N, Teranishi M, Yamaguchi Ｈ, Matsushita T, Watahiki MK, Tsuge T, Li SS, Hidema J
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  • Author(s): Izumi M, Hidema J, Ishida H
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  • Author(s): Ma H, Takahashi A, Yoshida Y, Adachi A, Kanai T, Ohno T, Nakano T.
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• [Journal Article] Targeting of Carbon Ion-Induced G2 Checkpoint Activation in Lung Cancer Cells Using Wee-1 Inhibitor MK-1775 (2015)
  • Author(s): Ma H, Takahashi A, Sejimo Y, Adachi A, Kubo N, Isono M, Yoshida Y, Kanai T, Ohno T, Nakano T.
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  • DOI: 10.1667/rr14171.1
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Genetic and phenotypic analyses of Calcineurin A subunit in Arthroderma vanbreuseghemii (2015)
  • Author(s): Alshahni MM, Shimizu K, Yoshimoto M, Yamada T, Nishiyama Y, Arai T, Makimura K
  • Journal Title: Med Mycol Volume: 54 Pages: 207-18
  • DOI: 10.1093/mmy/myv088
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Dermatophytosis due to Microsporum incurvatum: notification and identification of a neglected pathogenic species (2015)
  • Author(s): Rezaei-Matehkolaei A, Makimura K, Graser Y, Seyedmousavi S, Abastabar M, Rafiei A, Zhan P, Ronagh A, Jafarpour S
  • Journal Title: Mycopathologia Volume: 181 Pages: 107-13
  • DOI: 10.1007/s11046-015-9946-6
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Microbes and crewed space habitat (2015)
  • Author(s): Yamaguchi N, Nasu M
  • Journal Title: J Dis Res Volume: 10 Pages: 1022-4
• [Journal Article] Microbial observatory research in the International Space Station and Japanese Experiment Module "Kibo" (2015)
  • Author(s): Shirakawa M, Tanigaki F, Yamazaki T
  • Journal Title: J Dis Res Volume: 10 Pages: 1025-30
• [Journal Article] Significance of changes in the skin fungal microbiomes of astronauts staying on the International Space Station (2015)
  • Author(s): Sugita T, Cho O
  • Journal Title: J Dis Res Volume: 10 Pages: 1031-4
• [Journal Article] Bacterial Monitoring in the International Space Station (2015)
  • Author(s): Ichijo T, Yamaguchi N, nasu M
  • Journal Title: J Dis Res Volume: 10 Pages: 1035-9
• [Presentation] Design and synthesis of novel ligands of opioid receptors (2015)
  • Author(s): Nagase H
  • Organizer: Pacifichem
  • Place of Presentation: Honolulu, HI, USA
  • Year and Date: 2015-12-17
  • Int'l Joint Research / Invited
• [Book] 4Arch Pharm Chem Life Sci「Synthesis of novel triplets with a 1,3,5-trioxazatriquinane skeleton and their pharmacologies for opioid receptors」 (2015)
  • Author(s): Nagase H, Katsunuma N
  • Total Pages: 15
  • Publisher: Wiley
• [Book] Orexin and Sleep: Molecular, Functional and Clinical Aspects「Orexin and Metabolism」 (2015)
  • Author(s): Funato H
  • Total Pages: 18
  • Publisher: Springer
• [Book] 平成27年度日本薬学会医薬化学部会賞を受賞し、Med Chem Newsに掲載「低分子オレキシン受容体アゴニストの創製」 (2015)
  • Author(s): 斉藤毅、長瀬博
  • Total Pages: 7
  • Publisher: 日本薬学会
• [Book] メカノバイオロジー：細胞が力を感じ応答する仕組み (2015)
  • Author(s): 曽我部正博（編集）
  • Total Pages: 332
  • Publisher: 化学同人
• [Book] The Lipid, vol.27「Ⅲ.サルコぺニアの予防と治療、1.筋衛星細胞活性化による骨格筋再生」 (2015)
  • Author(s): 瀬原淳子
  • Total Pages: 6
  • Publisher: メディカルレビュー社
• [Book] 日本薬学会誌ファルマシア「オピニオン：メカノバイオロジーの可能性」 (2015)
  • Author(s): 曽我部正博
  • Total Pages: 3
  • Publisher: 日本薬学会
• [Book] 日本生物物理学会誌生物物理「アクチン線維は張力を感じ、コフィリンとの相互作用を介して細胞骨格の動態を制御するメカノセンサーである」 (2015)
  • Author(s): 辰巳仁史、早川公英、曽我部正博
  • Total Pages: 5
  • Publisher: 日本生物物理学会
• [Book] 血管医学「発展するメカノセンシング研究」 (2015)
  • Author(s): 曽我部正博
  • Total Pages: 13
  • Publisher: メディカルレビュー社
• [Book] JOHNS「起立性調節障害に自律神経はどう関与するか？」 (2015)
  • Author(s): 森田啓之
  • Total Pages: 4
  • Publisher: 東京医学社
• [Book] PROGRESS IN MEDICINE「フレイルと骨粗鬆症の関連」 (2015)
  • Author(s): 梶博史
  • Total Pages: 4
  • Publisher: ライフサイエンス
• [Book] 循環制御「長期宇宙滞在時に解決すべき医学的課題～循環制御関連を中心に～」 (2015)
  • Author(s): 古川聡
  • Total Pages: 3
  • Publisher: 日本循環制御医学会
• [Remarks] 宇宙に生きる 宇宙からひも解く新たな生命制御機構の統合的理
  • URL: http://living-in-space.jp/
• [Funded Workshop] International Symposium on LIVING IN SPACE (2017)
  • Place of Presentation: Tokyo