GPCRシグナルを合理的に調節するためのモデルセルを設計する
William M Shaw1, Hitoshi Yamauchi2, Jack Mead2
1Department of Bioengineering, Imperial College London, London SW7 2AZ, UK; Centre for Synthetic Biology, Imperial College London, London SW7 2AZ, UK.
Cell
|April 9, 2019
まとめ
科学者たちは 予想可能な細胞反応のために 酵母で合成Gタンパク質結合受容体 (GPCR) システムを設計しました このモジュラーシステムはペプチド,メタボリート,ホルモンの検出のための細胞センサーの正確な調整を可能にします.
科学分野:
- 分子生物学
- 合成生物学
- セルラー・シグナル
背景:
- Gタンパク質結合受容体 (GPCRs) は環境のシグナルに対する細胞反応を媒介するが,そのシグナル伝達は複雑で,自然な変化のために予測が難しい.
- 自然なGPCR信号伝達経路の多様な構造と発現は,予測可能な刺激-反応関係を阻害する.
研究 の 目的:
- 合成生物学のツールを用いて予測可能で調整可能なGPCRシグナルシステムを設計する.
- GPCR媒介細胞反応を合理的に制御するための設計原理を特定する.
- 特定のセンシングアプリケーションのためのセルとコンソーシアムのエンジニアリングを可能にします.
主な方法:
- 酵母でゲノム工学を用いて 隔離されたモジュラーGPCR信号伝達システムを構築した.
- 重要なシグナリングコンポーネントの貢献を定義するために,計算および実験的リファクタリングを使用した.
- 5つの異なるGPCRを使用してシステムをテストし,調整可能な用量反応を示しました.
主要な成果:
- 予測可能な用量反応調整能力を有する合成GPCRシステムを成功裏に構築した.
- 刺激に対する細胞の感受性を合理的に制御するための単純な設計原理を特定した.
- ペプチド,メタボリート,ホルモンの特定の濃度に対応する酵母細胞とコンソーシアムのエンジニアリングを実証した.
結論:
- 開発されたモジュラーGPCRシステムは,細胞センサーの合理的なチューニングを可能にします.
- この枠組みは,様々な生物系におけるGPCRベースのシグナリングを再プログラムするための基礎を提供します.
- 設計されたシステムは 人間の健康に 関連する分子の検出に 潜在的応用があります
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