| Project/Area Number |
18K19476
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 50:Oncology and related fields
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| Research Institution | Osaka University |
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Principal Investigator |
FUJIWARA Tomoko 大阪大学, 放射線科学基盤機構附属ラジオアイソトープ総合センター, 特任研究員(常勤) (70402922)
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| Project Period (FY) |
2018-06-29 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | stem cell competition / 細胞間相互作用 / ゲノム編集技術 / メダカ / 損傷応答 / 発がん / 高発がん個体 / 体細胞モザイク |
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| Outline of Final Research Achievements |
Mutagenesis is a terminal biological effect of various DNA damage stresses and a critical factor of carcinogenesis. It has been reported that carcinogenesis can be suppressed even if the Driver mutation required for carcinogenesis occurs. Stem cells competition has been proposed as one of the factors of tumor suppression. We have tried to establish the detection system for genes involved in Stem cells competition. We established three mutants required for this system, tumor suppressor gene (Bap1), regulation factor for cell differentiation signal (Notch1a), cell adhesion factor (Fat1a), by CRISPR. We have also constructed a BAC vector which enable to introduce deletion mutation of the target gene in mosaic expression pattern, and have confirmed that the vector can generate proper deletion mutation in vitro.
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| Academic Significance and Societal Importance of the Research Achievements |
がんは我が国を含む先進国において常に死因の上位を占める疾患で、stem cell competitionはその発症の成否に関与する重要な現象である。本研究では、これに関与する遺伝子の検出系確立のために必要な遺伝子変異体をメダカにおいて作製し、さらにこれら遺伝子の正常、異常アリルを同一個体内でモザイク状に発現させることを可能にするBAC vectorを作製することができた。今後、本系の完成により当該分野のみならず広く生物・医学分野で極めて大きな役割を果たすと考えられる。
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