| Project/Area Number |
17H00783
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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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 | Nagoya University |
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Principal Investigator |
OGI Tomoo 名古屋大学, 環境医学研究所, 教授 (80508317)
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| Co-Investigator(Kenkyū-buntansha) |
光武 範吏 長崎大学, 原爆後障害医療研究所, 教授 (50404215)
真下 知士 大阪大学, 医学系研究科, 准教授 (80397554)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥42,770,000 (Direct Cost: ¥32,900,000、Indirect Cost: ¥9,870,000)
Fiscal Year 2019: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2018: ¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000)
Fiscal Year 2017: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
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| Keywords | ゲノム不安定性疾患 / DNA修復 / DNA損傷応答 / 次世代オミクス解析 / 転写共役修復 (TC-NER) / 修復 |
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| Outline of Final Research Achievements |
We have investigated on human genetic disorders associated with genome instability. Patients with these syndromes have developed various clinical manifestations due to malfunctions of DNA repair and damage response system. We have collected undiagnosed cases and tried to elucidate the genetic cause of diseases using the Multi-omics approach that involves next-generation sequencing, high-accurate mass spectrometry, and precise DNA repair assays. Once we identified pathogenic variants, we have performed in vitro and in vivo analyses as well as animal studies so that we could get new insights into the molecular pathogenesis of the diseases. Recently, we have reported a detailed molecular mechanism of the initiation of transcription-coupled repair, which is compromised in Cockayne syndrome.
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| Academic Significance and Societal Importance of the Research Achievements |
ゲノム不安定性疾患群とは、DNA修復・損傷応答システムの先天異常により発症する疾患の総称であり、多数の疾患が含まれ、また各々の病態が類似することから臨床診断に難渋することも多い。オミクス解析により、ゲノム不安定性疾患の発症メカニズムを遺伝子・分子レベルで詳細に理解することは、難病患者の確定診断技術の開発や疾患緩和薬/治療薬開発へ寄与するとともに、ゲノムの安定維持機構の作動原理の理解を通して、がんや老化といった人類が直面している医学上の未解決課題に挑戦する上で欠かすことのできない基礎科学知識の蓄積に貢献することが可能である。
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