The prediction of the clinical records for infectious diseases by tracking the diversity of Immuoglobulin gene mutation
Project/Area Number |
16K14650
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Medical genome science
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Research Institution | National Institutes of Biomedical Innovation, Health and Nutrition |
Principal Investigator |
YASUI TERUHITO 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 感染症制御プロジェクト, プロジェクトリーダー (60283074)
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Co-Investigator(Kenkyū-buntansha) |
奥崎 大介 大阪大学, 微生物病研究所, 助教 (00346131)
南谷 武春 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 感染症制御プロジェクト, プロジェクト研究員 (00374679)
中村 昇太 大阪大学, 微生物病研究所, 特任准教授(常勤) (90432434)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | イムノグロブリン / 体細胞突然変異 / 破傷風毒素 / サイトメガロウイルス / 次世代シークエンサー / 感染症 / 遺伝子 |
Outline of Final Research Achievements |
Human acquired immune responses includes B cell differentiation in which immunoglobulin (Ig) genes undergo somatic mutations against pathogen infection. However, it has not been understood how fast and ordered Ig gene got mutations in response to the infections. To elucidate molecular mechanisms in which the human immune responses regulates Ig affinity, pathogen-induced Ig gene mutation was analyzed with molecular biological approach. As a result, we were able to identify the numbers and hot spots in the Ig gene mutations induced by vaccine components, and viral proteins derived from persistent infections. Collectively, the findings in this project indicate persistently viral infection always maintains the humoral immune responses through the continuous stimulation by viral proteins that the reactivation provides in human.
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Academic Significance and Societal Importance of the Research Achievements |
ヒトにおける感染に関する疫学的調査と、抗体遺伝子変異解析や抗体親和性解析といった、分子生物学的アプローチによってなされる融合研究である。一方、抗体遺伝子変異解析によって得られた知見を基に、規則性が見いだせれば、環境応答と遺伝子変異の相関性といった生命科学に新たなパラダイムを生むこととなる。また病原体にいつ感染したのかという予想が行えれば、本研究成果の発展型として、網羅的なIg遺伝子変異による「感染プロファイル」が可能となる。
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Report
(4 results)
Research Products
(32 results)
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[Journal Article] A mouse model of Epstein-Barr virus LMP1 and LMP2A driven germinal center B-cell lymphoproliferative disease.2017
Author(s)
1Minamitani, T., Ma, Y., Zhou, H., Kida, H., Tsai, C.-Y., Obana, M., Okuzaki, D., Fujio, Y., Kumanogoh, A., Kikutani, H., Zhao, B., Kieff, E., Gewuz, B. E., Yasui, T.
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Journal Title
Proc. Natl. Acad. Sci. USA.
Volume: 印刷中
Issue: 18
Pages: 4751-4756
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment.2017
Author(s)
Kitagawa Y, Ohkura N, Kidani Y, Vandenbon A, Hirota K, Kawakami R, Yasuda K, Motooka D, Nakamura S, Kondo M, Taniuchi I, Kohwi-Shigematsu T, Sakaguchi S.
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Journal Title
Nat Immunol.
Volume: 18(2)
Issue: 2
Pages: 173-183
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Argininosuccinate Synthase 1-Deficiency Enhances the Cell Sensitivity to Arginine through Decreased DEPTOR Expression in Endometrial Cancer.2017
Author(s)
Ohshima K, Nojima S, Tahara S, Kurashige M, Hori Y, Hagiwara K, Okuzaki D, Oki S, Wada N, Ikeda JI, Kanai Y, Morii E.
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Journal Title
Sci Rep
Volume: 7
Issue: 1
Pages: 45504-45504
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Crystal structure of the ADP-ribosylating component of BEC, the binary enterotoxin of Clostridium perfringens.2016
Author(s)
Kawahara K, Yonogi S, Munetomo R, Oki H, Yoshida T, Kumeda Y, Matsuda S, Kodama T, Ohkubo T, Iida T, Nakamura S
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Journal Title
Biochem Biophys Res Commun
Volume: 480
Issue: 2
Pages: 261-267
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The RNA Binding Protein Mex-3B Is Required for IL-33 Induction in the Development of Allergic Airway Inflammation.2016
Author(s)
Yamazumi Y, Sasaki O, Imamura M, Oda T, Ohno Y, Shiozaki-Sato Y, Nagai S, Suyama S, Kamoshida Y, Funato K, Yasui T, Kikutani H, Yamamoto K, Dohi M, Koyasu S, Akiyama T.
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Journal Title
Cell Rep.
Volume: 16
Issue: 9
Pages: 2456-2471
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Dysbiosis contributes to arthritis development via activation of autoreactive T cells in the intestine.2016
Author(s)
Maeda Y, Kurakawa T, Umemoto E, Motooka D, Ito Y, Gotoh K, Hirota K, Matsushita M, Furuta Y, Narazaki M, Sakaguchi N, Kayama H, Nakamura S, Iida T, Saeki Y, Kumanogoh A, Sakaguchi S, and Takeda K
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Journal Title
Arthritis Rheum
Volume: 68
Issue: 11
Pages: 2646-2661
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Homo-trimeric Structure of the Type IVb Minor Pilin CofB Suggests Mechanism of CFA/III Pilus Assembly in Human Enterotoxigenic Escherichia coli.2016
Author(s)
Kawahara K, Oki H, Fukakusa S, Yoshida T, Imai T, Maruno T, Kobayashi Y, Motooka D, Iida T, Ohkubo T, Nakamura S.
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Journal Title
J Mol Biol.
Volume: 428
Issue: 6
Pages: 1209-26
DOI
Related Report
Peer Reviewed
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[Journal Article] Polarization of M2 macrophages requires Lamtor1 that integrates cytokine and amino-acid signals2016
Author(s)
Kimura T, Nada S, Takegahara N, OkunoT, NojimaS, Kang S, Ito D, Morimoto K, Morimoto K, Hosokawa T, Hayama Y, Mitsui Y, Sakurai N, Sarashina-Kida H, Nishide M, Maeda Y, Takamatsu H, Okuzaki D, Yamada M, Okada M, Kumanogoh A.
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Journal Title
Nat Commun.
Volume: 7
Issue: 1
Pages: 13130-13130
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] The concerted impact of Epstein-Barr Virus LMP1 and LMP2A on the virus-induced lymphoproliferative diseases in mouse model.2017
Author(s)
Takeharu Minamitani, Yjie Ma, Hufeng Zhou, Hiroshi Kida, Chao-Yuan Tsai, Masanori Obana, Daisuke Okuzaki, Yasushi Fujio, Atsushi Kumanogoh, Bo Zhao, Hiroshi Kikutani, Elliott Kieff, Benjamin E Gewurz, Terihito Yasui.
Organizer
第42回国際ヘルペスウイルスワークショップ2017
Related Report
Int'l Joint Research
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