Elucidation of mechanisms linking between molecular behavior and activation as a basis for in-cell single-molecule screening
| Project/Area Number |
18H01839
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 28040:Nanobioscience-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Hiroshima Michio 国立研究開発法人理化学研究所, 生命機能科学研究センター, 上級研究員 (20392087)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | 1分子イメージング / 細胞内シグナル伝達 / 薬剤スクリーニング / １分子イメージング・ナノ計測 / １分子生体情報学 / 1分子生体情報学 |
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| Outline of Final Research Achievements |
Epidermal growth factor receptor (EGFR), which transmits primarily cell proliferation signals into cells after binding with an extracellular cytokine, concerns with critical diseases such as cancers. However, how EGFR regulates the cell responses through its molecular behavior remains unrevealed. In this study, we measured EGFR behaviors of both wild type and cancerous mutants by single-molecule imaging in cells and succeeded to detect changes in the molecular structures from the mobilities. Not only effects of anti-cancer drugs on EGFR but also the resistance of mutants against drugs were reflected in the behaviors. Furthermore, the activity of downstream signaling could be read out from the oligomerization of EGFR. The findings in the study will be a basis for a novel drug screening.
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| Academic Significance and Societal Importance of the Research Achievements |
細胞内の注目する分子を一つ一つイメージングする技術により計測した分子のふるまいから、抗癌剤などの薬剤が分子の活性化に与える影響を定量的に解析できる。本研究では、分子の動態がどのように活性化レベルを反映するか、そのメカニズムの解明に取り組んだ。新しく得られた知見から、1分子解析データには分子の構造や反応だけでなく、細胞膜環境や細胞応答の程度など想定を超える情報が含まれていることが分かった。この計測・解析手法をロボティクスやAIにより自動化し大規模解析を可能とすれば、新規の薬剤スクリーニング法として応用できることが示唆された。
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Report
(4 results)
Research Products
(19 results)
