使用合成切割受体设计定制的细胞传感和响应行为
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
概括
研究人员使用仿真受体设计了合成Notch (synNotch) 途径. 这些新的途径使得可定制的细胞间通信和可编程的细胞行为能够适用于各种应用.
科学领域:
- 细胞生物学
- 合成生物学
- 分子工程
背景情况:
- 隙蛋白是细胞间通信至关重要的跨膜受体,通过膜内蛋白解调节信号.
- 诺奇途径涉及连接体结合,受体分裂和细胞内域释放以调节基因表达.
研究的目的:
- 使用合成Notch (synNotch) 平台设计新的细胞与细胞接触信号通路.
- 证明synNotch途径在哺乳动物细胞中驱动用户定义的功能反应的能力.
- 探索使用直角synNotch受体的组合信号和复杂细胞行为的潜力.
主要方法:
- 通过替换原生Notch的细胞外和细胞内域来构建嵌合的Notch受体.
- 在不同类型的哺乳动物中测试synNotch通路的功能.
- 使用正交的synNotch受体进行组合信号和集成的细胞反应.
主要成果:
- 化学synNotch受体成功产生了新的细胞接触信号通路.
- 通过SynNotch途径,可以诱导特定的,用户定义的细胞功能.
- 单个synNotch路径在功能上是正交的,允许独立操作.
- 结合使用synNotch受体使得布尔逻辑和多细胞级联等复杂的行为成为可能.
结论:
- 合成痕受体提供了一个多功能平台,用于设计定制的细胞感应和反应行为.
- SynNotch 技术可以灵活地设计响应特定细胞外线索的新信号通路.
- 这种方法可以精确控制细胞功能,并创建复杂的多细胞系统.
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