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: 20H05615
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• 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): 2020-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
• Keywords: 宇宙 / 無重力 / ストレス / 放射線 / 微生物 / 特殊環境 / 社会医学 / 微小重力

Outline of Research at the Start

月・火星への有人探査計画が進む中、宇宙極限環境での生体変化に関し、無重力、閉鎖環境、宇宙放射線・微生物環境リスクを重点的に取り上げて学際的チームで臨み、分子・細胞レベルからヒトの高次制御まで統合的理解を深め、これらリスクの複合的効果など未知の領域にも挑戦し、宇宙を切口にした新しい研究領域「宇宙に生きる」を創った。得られた知見は、地上の超高齢化・高ストレス社会を克服するための方策として応用できる。

Outline of Annual Research Achievements

長期宇宙滞在時、無重力の物理ストレスは筋萎縮や骨密度低下を、閉鎖環境の精神的ストレスは体内リズム不調を、放射線被ばく等の環境リスクはDNA変異等をきたす。有人宇宙探査で超長期宇宙滞在に挑戦する時代にあり、これらは解決すべき課題である。同時にこれら課題への深い理解は、地上の高齢化・ストレス社会における生命維持・恒常性の担保に貢献し、健康長寿社会につながる。
本領域では、11の計画研究と30の公募研究の相乗的展開で下記3プロジェクトに体系化し、地球上の生命体が有する恒常性維持と破綻に関する統一的理解に努めた。成果取りまとめの2020年度に新たに38報の論文が発行された。
1)重力影響による骨・筋・前庭・循環系・免疫機能の恒常性維持と破綻-細胞からモデル小動物、線虫、メダカ、ゼブラフィッシュ、マウスを用いた宇宙実験、過重力実験、さらには宇宙長期滞在の宇宙飛行士の影響などについて研究を進めた。細胞、組織から器官、それらのネットワーク、個体レベルで、それぞれ重力感受と適応応答機構ならびにその分子基盤を特定した。
2)閉鎖環境による「睡眠・心身の恒常性維持と破綻」-主にマウスとヒトを対象にした研究を展開し、重力影響では体循環調節機能に影響が現れるが、閉鎖環境ストレスではその影響はみられず、一方で脳循環調節機能を減弱させること、脳血流の変化、更に新たなストレスマーカー候補を検討した。また、ストレスと関連が深い睡眠・覚醒の領域においては新たな睡眠診断デバイス、不眠症治療薬の評価分析、眠気の分子的実体を捉えるなど世界トップレベルでの研究を展開・達成することができた。
3)微生物や宇宙放射線など外部環境リスクによる「生体の恒常性維持と破綻」-無重力と閉鎖環境を組み合わせた複合影響を研究するため、新規装置開発、メタゲノム解析、蛍光プローブやバイオイメージングなど新たなモニタリングシステムの開発も行った。

Research Progress Status

令和2年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和2年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] バージニア大学/コロラド州立大学/Prairie View A&M University(米国)
• [Int'l Joint Research] ドイツ航空宇宙センター(ドイツ)
• [Int'l Joint Research] パスツール研究所(フランス)
• [Int'l Joint Research] バルセロナ大学/Pompeu Fabra University(スペイン)
• [Int'l Joint Research] ベルゲン大学(ノルウェー)
• [Int'l Joint Research]
• [Journal Article] GABA from vasopressin neurons regulates the time at which suprachiasmatic nucleus molecular clocks enable circadian behavior (2021)
  • Author(s): Maejima Takashi、Tsuno Yusuke、Miyazaki Shota、Tsuneoka Yousuke、Hasegawa Emi、Islam Md Tarikul、Enoki Ryosuke、Nakamura Takahiro J.、Mieda Michihiro
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 118 Issue: 6 Pages: 1-18
  • DOI: 10.1073/pnas.2010168118
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• [Journal Article] Identification of fungi isolated from astronaut nasal and pharyngeal smears and saliva (2021)
  • Author(s): Kazuo Satoh , Takashi Yamazaki , Satoshi Furukawa , Chiaki Mukai , Koichi Makimura
  • Journal Title: Microbiol Immunol Volume: 65 Issue: 2 Pages: 89
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• [Journal Article] Self‐Emergent Protocells Generated in an Aqueous Solution with Binary Macromolecules through Liquid‐Liquid Phase Separation (2020)
  • Author(s): Sakuta Hiroki, Fujita Fumika, Hamada Tsutomu, Hayashi Masahito, Takiguchi Kingo, Tsumoto Kanta, Yoshikawa Kenichi
  • Journal Title: ChemBioChem Volume: 21 Issue: 23 Pages: 3323-3328
  • DOI: 10.1002/cbic.202000344
  • NAID: 120006940266
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• [Journal Article] Ubiquitin ligase Cbl-b and inhibitory Cblin peptides (2020)
  • Author(s): Takeshi Nikawa, Kazumi Ishidoh
  • Journal Title: BBA - Proteins and Proteomics Volume: 1868 Issue: 11 Pages: 140495-140495
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• [Journal Article] How does spaceflight affect acquired immune system? (2020)
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  • Author(s): Ihara Dai、Watanabe Yusuke、Seya Daiki、Arai Yuji、Isomoto Yoshie、Nakano Atsushi、Kubo Atsushi、Ogura Toshihiko、Kawamura Teruhisa、Nakagawa Osamu
  • Journal Title: Developmental Biology Volume: 461 Issue: 2 Pages: 124-131
  • DOI: 10.1016/j.ydbio.2020.02.001
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• [Journal Article] Myelination during fracture healing in vivo in myelin protein zero (p0) transgenic medaka line (2020)
  • Author(s): Dodo Y, Chatani M, Azetsu Y, Hosonuma M, Karakawa A, Sakai N, Negishi-Koga T, Tsuji M, Inagaki K, Kiuchi Y, Takami M
  • Journal Title: Bone Volume: 133 Pages: 115225-115225
  • DOI: 10.1016/j.bone.2020.115225
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• [Journal Article] Generation and evaluation of a transgenic zebrafish for tissue-specific expression of a dominant-negative Rho-associated protein kinase-2. (2020)
  • Author(s): Iida A, Wang Z, Hondo E, Sehara-Fujisawa A.
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• [Journal Article] Effects of N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine) on bone homeostasis in mice (2020)
  • Author(s): Kiyohara S, Sakai N, Handa K, Yamakawa T, Ishikawa K, Chatani M, Karakawa A, Azetsu Y, Munakata M, Ozeki M, Negishi-Koga T, Takami M
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• [Journal Article] Long-duration spaceflight alters estimated intracranial pressure and cerebral blood velocity (2020)
  • Author(s): Ken-ichi Iwasaki, Yojiro Ogawa, Takuya Kurazumi, Syed M. Imaduddin, Chiaki Mukai, Satoshi Furukawa, Ryo Yanagida, Tomokazu Kato, Toru Konishi, Ari Shinojima, Benjamin D. Levine, Thomas Heldt
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• [Journal Article] Early high-fat feeding improves histone modifications of skeletal muscle at middle-age in mice. (2020)
  • Author(s): Yoshie T, Saito C, Kawano F
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• [Journal Article] Roles of olfactomedin 1 in muscle and bone alterations induced by gravity change in mice (2020)
  • Author(s): Shimode T, Kawao N, Morita H, Ishida M, Takafuji Y, Kaji H
  • Journal Title: Calcified Tissue International Volume: 27 Issue: 2 Pages: 180-190
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• [Journal Article] Utriculo-ocular pathway dysfunction is more frequent in vestibular migraine than probable vestibular migraine. (2020)
  • Author(s): Fujimoto C, Kamogashira T, Takenouchi S, Kinoshita M, Sugasawa K, Kawahara T, Yamasoba T, Iwasaki S
  • Journal Title: J Neurol Volume: 267 Issue: 8 Pages: 2340-2346
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• [Journal Article] Peripherally administered cisplatin activates a parvocellular neuronal subtype expressing arginine vasopressin and enhanced green fluorescent protein in the paraventricular nucleus of a transgenic rat (2020)
  • Author(s): Akiyama Yasuki、Yoshimura Mitsuhiro、Ueno Hiromichi、Sanada Kenya、Tanaka Kentaro、Sonoda Satomi、Nishimura Haruki、Nishimura Kazuaki、Motojima Yasuhito、Saito Reiko、Maruyama Takashi、Hirata Keiji、Uezono Yasuhito、Ueta Yoichi
  • Journal Title: The Journal of Physiological Sciences Volume: 70 Issue: 1 Pages: 14558-14558
  • DOI: 10.1186/s12576-020-00764-z
  • Peer Reviewed / Open Access
• [Journal Article] Discovery of attenuation effect of orexin 1 receptor to aversion of nalfurafine: Synthesis and evaluation of D-nor-nalfurafine derivatives and analyses of the three active conformations of nalfurafine (2020)
  • Author(s): Nagumo Yasuyuki、Katoh Koki、Iio Keita、Saitoh Tsuyoshi、Kutsumura Noriki、Yamamoto Naoshi、Ishikawa Yukiko、Irukayama-Tomobe Yoko、Ogawa Yasuhiro、Baba Takeshi、Tanimura Ryuji、Yanagisawa Masashi、Nagase Hiroshi
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 30 Issue: 17 Pages: 127360-127360
  • DOI: 10.1016/j.bmcl.2020.127360
  • Peer Reviewed / Open Access
• [Journal Article] Loss of the conserved PKA sites of SIK1 and SIK2 increases sleep need (2020)
  • Author(s): Park Minjeong, Miyoshi Chika, Fujiyama Tomoyuki, Kakizaki Miyo, Ikkyu Aya, Honda Takato, Choi Jinhwan, Asano Fuyuki, Mizuno Seiya, Takahashi Satoru, Yanagisawa Masashi, Funato Hiromasa
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 8676-8676
  • DOI: 10.1038/s41598-020-65647-0
  • NAID: 120007163335
  • Peer Reviewed / Open Access
• [Journal Article] Myonectin inhibits the differentiation of osteoblasts and osteoclasts in mouse cells (2020)
  • Author(s): Kawaguchi M, Kawao N, Takafuji Y, Ishida M, Kaji H.
  • Journal Title: Heliyon. Volume: 6 Issue: 5 Pages: e03967-e03967
  • DOI: 10.1016/j.heliyon.2020.e03967
  • Peer Reviewed / Open Access
• [Journal Article] Extracellular vesicles secreted from mouse muscle cells suppress osteoclast formation: Roles of mitochondrial energy metabolism. (2020)
  • Author(s): Takafuji Y, Tatsumi K, Ishida M, Kawao N, Okada K, Kaji H.
  • Journal Title: Bone Volume: 134 Pages: 115298-115298
  • DOI: 10.1016/j.bone.2020.115298
  • Peer Reviewed / Open Access
• [Journal Article] VGLUT2-expressing neurons in the vestibular nuclear complex mediate gravitational stress-induced hypothermia in mice (2020)
  • Author(s): Abe C, Yamaoka Y, Maejima Y, Mikami T, Yokota S, Yamanaka A, Morita H
  • Journal Title: Communications Biology Volume: 227 Issue: 1 Pages: 1-13
  • DOI: 10.1038/s42003-020-0950-0
  • Peer Reviewed / Open Access
• [Journal Article] Adaptive responses of histone modifications to resistance exercise in human skeletal muscle (2020)
  • Author(s): Lim Changhyun、Shimizu Junya、Kawano Fuminori、Kim Hyo Jeong、Kim Chang Keun
  • Journal Title: PLOS ONE Volume: 15 Issue: 4 Pages: e0231321-e0231321
  • DOI: 10.1371/journal.pone.0231321
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Roles of Dkk2 in the linkage from muscle to bone during mechanical unloading in mice (2020)
  • Author(s): Kawao N, Morita H, Iemura S, Ishida M, Kaji H
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 7 Pages: 2547-2547
  • DOI: 10.3390/ijms21072547
  • Peer Reviewed / Open Access
• [Journal Article] A new method with an explant culture of the utricle for assessing the influence of exposure to low frequency noise on the vestibule (2020)
  • Author(s): Ohgami N, He T, Negishi-Oshino R, Gu Y, Li X, Kato M
  • Journal Title: J Toxicol Environ Health, Part A Volume: 83(5) Issue: 5 Pages: 215-218
  • DOI: 10.1080/15287394.2020.1746945
  • NAID: 120006869634
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Combined Environment Simulator for Low-Dose-Rate Radiation and Partial Gravity of Moon and Mars (2020)
  • Author(s): Takahashi Akihisa、Yamanouchi Sakuya、Takeuchi Kazuomi、Takahashi Shogo、Tashiro Mutsumi、Hidema Jun、Higashitani Atsushi、Adachi Takuya、Zhang Shenke、Guirguis Fady Nagy Lotfy、Yoshida Yukari、Nagamatsu Aiko、Hada Megumi、Takeuchi Kunihito、Takahashi Tohru、Sekitomi Yuji
  • Journal Title: Life Volume: 10 Issue: 11 Pages: 274-274
  • DOI: 10.3390/life10110274
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Simultaneous Exposure of Cultured Human Lymphoblastic Cells to Simulated Microgravity and Radiation Increases Chromosome Aberrations (2020)
  • Author(s): Sakuya Yamanouchi, Jordan Rhone, Jian-Hua Mao, Keigi Fujiwara, Premkumar B. Saganti, Akihisa Takahashi, and Megumi Hada
  • Journal Title: life Volume: 10(9) Issue: 9 Pages: 187-187
  • DOI: 10.3390/life10090187
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Targeted Central Nervous System Irradiation of Caenorhabditis elegans Induces a Limited Effect on Motility (2020)
  • Author(s): Suzuki Michiyo, Soh Zu, Yamashita Hiroki, Tsuji Toshio, Funayama Tomoo
  • Journal Title: Biology Volume: 9 Issue: 9 Pages: 289-289
  • DOI: 10.3390/biology9090289
  • Peer Reviewed / Open Access
• [Journal Article] Early induction and increased risk of precursor B-cell neoplasms after exposure of infant or young-adult mice to ionizing radiation (2020)
  • Author(s): Hirotaka Tachibana1,3, Takamitsu Morioka1,*, Kazuhiro Daino1, Yi Shang1, Mari Ogawa1, Misuzu Fujita1, Akira Matsuura3,4, Hiroyuki Nogawa3,4, Yoshiya Shimada2,† and Shizuko Kakinuma1,*
  • Journal Title: Journal of radiation research Volume: 61(5) Issue: 5 Pages: 648-656
  • DOI: 10.1093/jrr/rraa055
  • Peer Reviewed / Open Access
• [Journal Article] Nrf2 contributes to the weight gain of mice during space travel (2020)
  • Author(s): Suzuki, T., et al., Koshiba, S. et al., Yamamoto, M.（合計37名、本研究者は18番目）
  • Journal Title: Communications Biology Volume: 3 Issue: 1 Pages: 496
  • DOI: 10.1038/s42003-020-01227-2
  • NAID: 120007161347
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The skin mycobiome of an astronaut during a 1-year stay on the International Space Station (2020)
  • Author(s): *Takashi Sugita , Takashi Yamazaki , Otomi Cho , Satoshi Furukawa and Chiaki Mukai
  • Journal Title: Medical Mycology Volume: N/A Issue: 1 Pages: 106-109
  • DOI: 10.1093/mmy/myaa067
  • Peer Reviewed
• [Journal Article] Chloroplast Autophagy and Ubiquitination Combine to Manage Oxidative Damage and Starvation Responses (2020)
  • Author(s): Kikuchi Yuta、Nakamura Sakuya、Woodson Jesse D.、Ishida Hiroyuki、Ling Qihua、Hidema Jun、Jarvis R. Paul、Hagihara Shinya、Izumi Masanori
  • Journal Title: Plant Physiology Volume: 183 Issue: 4 Pages: 1531-1544
  • DOI: 10.1104/pp.20.00237
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Iron Ladies - How Desiccated Asexual Rotifer Adineta vaga Deal With X-Rays and Heavy Ions? (2020)
  • Author(s): Hespeels B, Penninckx S, Cornet V, Bruneau L, Bopp C, Baumle V, Redivo B, Heuskin AC, Moeller R, Fujimori A, Stephane Lucas, Doninck KV.
  • Journal Title: frontiers in Microbiology Volume: 11 Pages: 1-14
  • DOI: 10.3389/fmicb.2020.01792
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• [Journal Article] The Responses of the Black Fungus Cryomyces Antarcticus to High Doses of Accelerated Helium Ions Radiation within Martian Regolith Simulants and Their Relevance for Mars (2020)
  • Author(s): Pacelli C, Cassaro A, Aureli L, Moeller R, Fujimori A, Onofri S.
  • Journal Title: life Volume: 10 Issue: 8 Pages: 1-14
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• [Journal Article] Insufficiency of ciliary cholesterol in hereditary Zellweger syndrome. (2020)
  • Author(s): Miyamoto T, Hosoba K, Itabashi T, Iwane AH, Akutsu AN, Ochiai H, Saito Y, Yamamoto T, Matsuura S
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  • DOI: 10.15252/embj.2019103499
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• [Journal Article] Space radiation biology for “Living in Space” (2020)
  • Author(s): Furukawa S, Nagamatsu A, Nenoi M, Fujimori A, Kakinuma S, Katsube T, Wang B, Tsuruoka C, Shirai T, Nakamura AJ, Sakaue-Sawano A, Miyawaki A, Harada H, Kobayashi M, Kobayashi J, Kunieda T, Funayama T, Suzuki M, Miyamoto T, Hidema J, Yoshida Y, Takahashi A.
  • Journal Title: BioMed Res Int. Volume: 2020 Issue: 1 Pages: 4703286-4703286
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• [Journal Article] Identification of a herpes simplex virus 1 gene encoding neurovirulence factor by chemical proteomics (2020)
  • Author(s): Kato Akihisa、Adachi Shungo、Kawano Shuichi、Takeshima Kousuke、Watanabe Mizuki、Kitazume Shinobu、Sato Ryota、Kusano Hideo、Koyanagi Naoto、Maruzuru Yuhei、Arii Jun、Hatta Tomohisa、Natsume Tohru、Kawaguchi Yasushi
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  • DOI: 10.1038/s41467-020-18718-9
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• [Journal Article] Growth and physiological characteristics of wasabi plantlets cultured by photoautotrophic micropropagation at different temperatures (2020)
  • Author(s): Nhung Ngoc Hoang, Yoshiaki Kitaya, Toshio Shibuya, Ryosuke Endo
  • Journal Title: Plant Cell, Tissue and Organ Culture Volume: 143 Issue: 1 Pages: 87-96
  • DOI: 10.1007/s11240-020-01898-z
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Phosphoregulation of a Conserved Herpesvirus Tegument Protein by a Virally Encoded Protein Kinase in Viral Pathogenicity and Potential Linkage between Its Evolution and Viral Phylogeny (2020)
  • Author(s): Shibazaki Misato、Kato Akihisa、Takeshima Kosuke、Ito Jumpei、Suganami Mai、Koyanagi Naoto、Maruzuru Yuhei、Sato Kei、Kawaguchi Yasushi
  • Journal Title: Journal of Virology Volume: 94 Issue: 18 Pages: 1-4
  • DOI: 10.1128/jvi.01055-20
  • Peer Reviewed / Open Access
• [Presentation] 中枢時計におけるバソプレシン産生ニューロンの機能 (2020)
  • Author(s): 三枝理博
  • Organizer: 第27回日本時間生物学会学術大会
  • Invited
• [Presentation] Carbon-ion Cancer Radiotherapy: Double-Strand DNA Break Distribution and Repair (2020)
  • Author(s): Dylan J. Buglewicz, Hirokazu Hirakawa, Akira Fujimori, Takamitsu Kato
  • Organizer: The 66th RRS Annual Meeting
  • Int'l Joint Research
• [Presentation] High LET-like radiation tracks at the distal side of accelerated Proton Bragg peak (2020)
  • Author(s): Dakota Horendeck, Kade Walsh, Hirokazu Hirakawa, Akira Fujimori, Hisashi Kitamura, Takamitsu Kato
  • Organizer: The 66th RRS Annual Meeting
  • Int'l Joint Research
• [Presentation] Plant culture system as a water recycling device in space farming (2020)
  • Author(s): Kitaya Y
  • Organizer: JpGU Meeting 2020, A-OS25 陸域海洋相互作用-惑星スケール物質循環 Continental-Oceanic Mutual Interaction: Planetary scale Material Circulation
  • Int'l Joint Research
• [Book] 酸素環境感知の基本メカニズムとがん (2020)
  • Author(s): 小林稔、原田浩
  • Total Pages: 7
  • Publisher: 羊土社
  • ISBN: 9784758125321
• [Book] 第７章 宇宙植物工場の開発 第2 節 長期有人宇宙活動のための物質循環型植物工場 (2020)
  • Author(s): 北宅善昭，遠藤良輔
  • Total Pages: 7
  • Publisher: 技術情報協会
  • ISBN: 9784861048173
• [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解
  • URL: https://living-in-space.jaxa.jp/