宇宙からひも解く新たな生命制御機構の統合的理解

2020 Fiscal Year Annual Research Report

• Project Area: "LIVING IN SPACE" - Integral Understanding of life-regulation mechanism from "SPACE"
• Project/Area Number: 20H05615
• 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
• Keywords: 宇宙 / 無重力 / ストレス / 放射線 / 微生物

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)
  • Country Name: U.S.A.
  • Counterpart Institution: バージニア大学/コロラド州立大学/Prairie View A&M University
  • # of Other Institutions: 4
• [Int'l Joint Research] ドイツ航空宇宙センター(ドイツ)
  • Country Name: GERMANY
  • Counterpart Institution: ドイツ航空宇宙センター
• [Int'l Joint Research] パスツール研究所(フランス)
  • Country Name: FRANCE
  • Counterpart Institution: パスツール研究所
• [Int'l Joint Research] バルセロナ大学/Pompeu Fabra University(スペイン)
  • Country Name: SPAIN
  • Counterpart Institution: バルセロナ大学/Pompeu Fabra University
• [Int'l Joint Research] ベルゲン大学(ノルウェー)
  • Country Name: NORWAY
  • Counterpart Institution: ベルゲン大学
• [Int'l Joint Research]
  • # of Other Countries: 1
• [Journal Article] GABA from vasopressin neurons regulates the time at which suprachiasmatic nucleus molecular clocks enable circadian behavior (2021)
  • Author(s): Maejima T, Tsuno Y, Miyazaki S, Tsuneoka Y, Hasegawa E, Islam MT, Enoki R, Nakamura TJ, Mieda M
  • Journal Title: Proceedings of the National Academy of Sciences (PNAS) Volume: 118(6), Pages: e2010168118
  • DOI: 10.1073/pnas.2010168118
  • Peer Reviewed
• [Journal Article] Identification of fungi isolated from astronaut nasal and pharyngeal smears and saliva (2021)
  • Author(s): Satoh K, Yamazaki T, Furukawa S, Mukai C, Makimura K
  • Journal Title: Microbiology and Immunology Volume: 65(2) Pages: 89-94
  • DOI: 10.1111/1348-0421.12872
  • Peer Reviewed
• [Journal Article] Self‐Emergent Protocells Generated in an Aqueous Solution with Binary Macromolecules through Liquid‐Liquid Phase Separation (2020)
  • Author(s): Sakuta H, Fujita F Hamada T Hayashi M, *Takiguchi K (研究協力者), *Tsumoto K, Yoshikawa K (研究協力者)
  • Journal Title: ChemBioChem Volume: 21 Pages: 1-6
  • DOI: 10.1002/cbic.202000344
  • Peer Reviewed / Open Access
• [Journal Article] Ubiquitin ligase Cbl-b and inhibitory Cblin peptides (2020)
  • Author(s): Nikawa T, Ishidoh K
  • Journal Title: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics Volume: 1868 Pages: 140495
  • DOI: 10.1016/j.bbapap.2020.140495
  • Peer Reviewed / Open Access
• [Journal Article] How does spaceflight affect the acquired immune system? (2020)
  • Author(s): Akiyama T, Horie K, Hinoi E, Hiraiwa M, Kato A, Maekawa Y, Takahashi A, Furukawa S
  • Journal Title: NPJ Microgravity Volume: 6 Pages: 14
  • DOI: 10.1038/s41526-020-0104-1
  • Peer Reviewed / Open Access
• [Journal Article] Transient and lineage-restricted requirement of Ebf3 for sternum ossification (2020)
  • Author(s): Kuriki M, Sato F, Arai H, Sogabe M, Kaneko M, Kiyonari H, Kawakami K, Yoshimoto Y, Shukunami C, and Sehara-Fujisawa A
  • Journal Title: Development Volume: 147 Pages: dev186239
  • DOI: 10.1242/dev.186239
  • Peer Reviewed / Open Access
• [Journal Article] Expression of Hey2 transcription factor in the early embryonic ventricles is controlled through a distal enhancer by Tbx20 and Gata transcription factors (2020)
  • Author(s): Ihara D, Seya D, Arai Y, Isomoto Y, Nakano A, Kubo A, Ogura T, Kawamura T, Nakagawa O
  • Journal Title: Developmental Biology Volume: 461(2) Pages: 124-131
  • DOI: 10.1016/j.ydbio.2020.02.001
  • Peer Reviewed
• [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
  • DOI: 10.1016/j.bone.2020.115225
  • Peer Reviewed
• [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
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 525 Pages: 8-13
  • DOI: 10.1016/j.bbrc.2020.02.055
  • Peer Reviewed
• [Journal Article] Effects of N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine) on bone homeostasis in mice (2020)
  • Author(s): Kiyohara S, Sakai N, Handa K, Yamakawa T, Chatani M, Karakawa A, Azetsu Y, Munakata M, Ozeki M, Negishi-Koga Takako, *Takami M
  • Journal Title: Journal of Oral Biosciences Volume: 62(2) Pages: 131-138
  • DOI: 10.1016/j.job.2020.03.003
  • Peer Reviewed
• [Journal Article] Long-duration spaceflight alters estimated intracranial pressure and cerebral blood velocity (2020)
  • Author(s): Iwasaki K, Ogawa Y, Kurazumi T, Imaduddin SM, Mukai C, Furukawa S, Yanagida R, Kato T, Konishi T, Shinojima A, Levine BD, Heldt T
  • Journal Title: The Journal of Physiology Volume: 599(4) Pages: 1067-1081
  • DOI: 10.1113/jp280318
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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
  • Journal Title: Laboratory Animal Research Volume: 36 Pages: 25
  • DOI: 10.1186/s42826-020-00060-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Roles of olfactomedin 1 in muscle and bone alterations induced by gravity change in mice (2020)
  • Author(s): Shimoide T, Kawao N, Morita H, Ishida M, Takafuji Y, Kaji H
  • Journal Title: Calcified Tissue International Volume: 107 Pages: 180-190
  • DOI: 10.1007/s00223-020-00710-6
  • Peer Reviewed
• [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: Journal of Neurology Volume: 267 Pages: 2340-2346
  • DOI: 10.1007/s00415-020-09851-y.
  • Peer Reviewed
• [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 Y, Yoshimura M, Ueno H, Sanada K, Tanaka K, Sonoda S, Nishimura H, Nishimura K, Motojima Y, Saito R, Maruyama T, Hirata K, Uezono Y, Ueta Y
  • Journal Title: The Journal of Physiological Sciences Volume: 70 Pages: 9
  • 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): Y, Nagumo, K. Katoh, K. Iio, T. Saitoh, N. Kutsumura, N. Yamamoto, Y. Ishikawa, Y. Irukayama-Tomobe, Y. Ogawa, T. Baba, R. Tanimura, M. Yanagisawa, *H. Nagase
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 30 Pages: 127360
  • DOI: 10.1016/j.bmcl.2020.127360
  • Peer Reviewed
• [Journal Article] Loss of the conserved PKA sites of SIK1 and SIK2 increases sleep need (2020)
  • Author(s): Park M, Miyoshi C, Fujiyama T, Kakizaki M, Ikkyu A, Honda T, Choi J, Asano F, Mizuno S, Takahashi S, Yanagisawa M, Funato H
  • Journal Title: Scientific Reports Volume: 10 Pages: 8676
  • DOI: 10.1038/s41598-020-65647-0
  • 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 Pages: 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
  • 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: 3 Pages: 227
  • 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 CH, Shimizu J, Kawano F, Kim HJ, Kim CK
  • Journal Title: PLOS ONE Volume: 15 Pages: 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 Pages: 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, Oshino-Negishi R, Gu Y, Li X, Kato M
  • Journal Title: Journal of Toxicology and Environmental Health, Part A Volume: 83(5) Pages: 215-218
  • DOI: 10.1080/15287394.2020.1746945
  • Peer Reviewed
• [Journal Article] Combined-environment simulator for low-dose-rate radiation and partial gravity of Moon and Mars (2020)
  • Author(s): Takahashi A, Yamanouchi S, Takeuchi K, Takahashi S, Tashiro M, Hidema J, Higashitani A, Adachi T, Zhang S, Guirguis FNL, Yoshida Y, Nagamatsu A, Hada M, et al.
  • Journal Title: Life Volume: 10(11) Pages: E27
  • 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): Yamanouchi S, Rhone J, Mao JH, Fujiwara K, Saganti PB, Takahashi A, Hada M
  • Journal Title: Life Volume: 10(9) Pages: E187
  • 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 M, Soh Z, Yamashita H, Tsuji T, Funayama T
  • Journal Title: Biology Volume: 9 Pages: 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): Tachibana H, Morioka T, Daino K, Shang Y, Ogawa M, Fujita M, Matsuura A, Nogawa H, Shimada Y, Kakinuma S
  • Journal Title: Journal of Radiation Research Volume: 61(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, Uruno A, Yumoto A, Okada R, Kudo T, Kensler TW, Takahashi S, Yamamoto M et al.
  • Journal Title: Communications Biology Volume: 3(1) Pages: 496
  • DOI: 10.1038/s42003-020-01227-2
  • 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): Sugita T, Yamazaki T, Cho O, Furukawa S, Mukai C
  • Journal Title: Medical Mycology Volume: N/A Pages: myaa067
  • DOI: 10.1093/mmy/myaa067
  • Peer Reviewed
• [Journal Article] Chloroplast Autophagy and Ubiquitination Combine toManage Oxidative Damage andStarvation Responses (2020)
  • Author(s): Kikuchi Y, Nakamura S, Woodson JD, Ishida H, Ling Q, Hidema J, Jarvis RP, Hagihara S, Izumi M
  • Journal Title: Plant Physiology Volume: 183 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: 1792
  • DOI: 10.3389/fmicb.2020.01792
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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 Pages: 130
  • DOI: 10.3390/life10080130
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Insufficiency of ciliary cholesterol in hereditary Zellweger syndrome (2020)
  • Author(s): Miyamoto T, Hosoba K, Itabashi T, Iwane AH, Akutsu SN, Ochiai H, Saito Y, Yamamoto T, Matsuura S.
  • Journal Title: The EMBO Journal Volume: 39(12) Pages: e103499
  • DOI: 10.15252/embj.2019103499.
  • Peer Reviewed / Open Access
• [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 Research International Volume: 2020 Pages: 4703286
  • DOI: 10.1155/2020/4703286.eCollection 2020.
  • Peer Reviewed / Open Access
• [Journal Article] Identification of a Herpes Simplex Virus 1 Gene Encoding Neurovirulence Factor by Chemical Proteomics (2020)
  • Author(s): Kato A, Adachi S, Kawano S, Takeshima K, Watanabe M, Kitazume S, Sato R, Kusano H, Koyanagi N, Maruzuru Y, Arii J, Hatta T, Natsume T, Kawaguchi Y
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  • DOI: 10.1038/s41467-020-18718-9
  • Peer Reviewed / Open Access
• [Journal Article] Growth and physiological characteristics of wasabi plantlets cultured by photoautotrophic micropropagation at different temperatures (2020)
  • Author(s): Hoang NN, Kitaya Y, Shibuya T, Endo R
  • Journal Title: Plant Cell, Tissue and Organ Culture Volume: 143 Pages: 87-96
  • DOI: 10.1007/s11240-020-01898-z
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Phospho-regulation 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 M, Kato A, Takeshima K, Ito J, Suganami M, Koyanagi N, Maruzuru Y, Sato K, Kawaguchi Y
  • Journal Title: Journal of Virology Volume: 94 Pages: e01055-20
  • 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: 978-4-7581-2532-1
• [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: 978-4-86104-817-3
• [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/