合成ノッチ受容体を用いたカスタマイズされた細胞感知および応答行動
Leonardo Morsut1, Kole T Roybal1, Xin Xiong1
1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Center for Systems and Synthetic Biology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute.
Cell
|February 3, 2016
まとめ
研究者はキメリック受容体を用いて合成ノッチ (synNotch) 経路を設計した. これらの新しい経路は,カスタマイズされた細胞間の通信と プログラム可能な細胞の行動を 多様なアプリケーションに可能にします
科学分野:
- 細胞生物学
- 合成生物学
- 分子工学
背景:
- ノッチタンパク質は細胞間の通信に不可欠なトランスメブラン受容体であり,膜内タンパク質分解を通じて信号伝達を媒介する.
- Notch経路は,リガンド結合,受容体分裂,遺伝子発現を調節する細胞内ドメインの放出を含む.
研究 の 目的:
- 合成ノッチ (synNotch) プラットフォームを使用して新しい細胞-細胞接触シグナル経路を設計する.
- 哺乳類の細胞でユーザ定義の機能的反応を誘導する synNotch 経路の能力を実証する.
- オートゴーナル・シンノッチ受容体による結合信号伝達と複雑な細胞行動の可能性を調査する.
主な方法:
- ネイティブ・ノッチの細胞外および細胞内ドメインの置換により,キメリック・シンノッチ受容体の構築.
- 異なる哺乳類の細胞タイプで SynNotch経路の機能をテストする.
- 結合信号と統合された細胞応答のための正交のシンノッチ受容体を利用する.
主要な成果:
- キメリックシンノッチ受容体は,新しい細胞間接触シグナル伝達経路を成功裏に生成した.
- SynNotch経路は,特定の,ユーザー定義の細胞機能を誘導する能力を示しました.
- 個々のシンノッチ経路は機能的に正交であり,独立した操作を可能にしました.
- シンノッチ受容体の組み合わせにより,ブール論理や多細胞カスケードのような複雑な行動が可能になった.
結論:
- 合成ノッチ受容体は,カスタマイズされた細胞感知と応答行動を設計するための多用途のプラットフォームを提供します.
- SynNotch技術は,特定の細胞外信号に反応する新しい信号経路の設計に柔軟性を提供します.
- このアプローチにより 細胞の機能を正確に制御し 複雑な多細胞システムを 作り出すことができます
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