| Project/Area Number |
15K00543
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation and chemicals
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
阿部 悠 福島県立医科大学, 医学部, 助教 (00722472)
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| Project Period (FY) |
2015-10-21 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 低線量放射線 / 細胞応答 / メタボローム / 蛍光分子解析 / 蛍光分子分析 |
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| Outline of Final Research Achievements |
For the purpose of multidimensional understandings of intra-cellular environmental changes after low-dose ionizing radiation, we made multimodal analyses using molecular species-specific fluorescent probes and liquid chromatography-mass spectrometry.
After the knockdown of DNA damage response genes in human fibroblasts, we found the loss of alteration of nucleic acids metabolites and lipid derivatives which we reported previously, and loss of response in mitochondrial activity and redox state by low-dose irradiation.
In addition, we made a system of DNA sequence specific digestion using CRISPR/Cas9, and confirmed DNA damages and induction of mutation which corresponds to low dose irradiation.
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| Academic Significance and Societal Importance of the Research Achievements |
低線量放射線照射による細胞応答について、正常細胞の系統的なノックダウンによる同一の実験系を使い、DNA損傷応答シグナル伝達機構からの細胞内環境や代謝調節への関与を、複数の解析モードにより結果を得ることができた。特定のシグナル分子と細胞内環境を並行して解析できたことから、今後シグナルのクロストーク解析に有用であると考えられた。
また電離放射線を使わず、DNA二本鎖切断を誘導できるCRISPR/Cas9系を作成したことで、低線量で生じる反応を高感度に定量的に解析できる可能性が示された。
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