Cell Systems ( IF 9.0 ) Pub Date : 2022-03-16 , DOI: 10.1016/j.cels.2022.02.004 Dirk Benzinger 1 , Serguei Ovinnikov 1 , Mustafa Khammash 1
Cells live in constantly changing environments and employ dynamic signaling pathways to transduce information about the signals they encounter. However, the mechanisms by which dynamic signals are decoded into appropriate gene expression patterns remain poorly understood. Here, we devise networked optogenetic pathways that achieve dynamic signal processing functions that recapitulate cellular information processing. Exploiting light-responsive transcriptional regulators with differing response kinetics, we build a falling edge pulse detector and show that this circuit can be employed to demultiplex dynamically encoded signals. We combine this demultiplexer with dCas9-based gene networks to construct pulsatile signal filters and decoders. Applying information theory, we show that dynamic multiplexing significantly increases the information transmission capacity from signal to gene expression state. Finally, we use dynamic multiplexing for precise multidimensional regulation of a heterologous metabolic pathway. Our results elucidate design principles of dynamic information processing and provide original synthetic systems capable of decoding complex signals for biotechnological applications.
中文翻译:
合成基因网络概括了动态信号解码和差异基因表达
细胞生活在不断变化的环境中,并利用动态信号通路来转导有关它们遇到的信号的信息。然而,动态信号被解码为适当的基因表达模式的机制仍然知之甚少。在这里,我们设计了网络化的光遗传学途径,实现了概括细胞信息处理的动态信号处理功能。利用具有不同响应动力学的光响应转录调节因子,我们构建了一个下降沿脉冲检测器,并表明该电路可用于解复用动态编码的信号。我们将此解复用器与基于 dCas9 的基因网络相结合,以构建脉冲信号过滤器和解码器。应用信息论,我们表明,动态多路复用显着增加了从信号到基因表达状态的信息传输能力。最后,我们使用动态多路复用对异源代谢途径进行精确的多维调控。我们的结果阐明了动态信息处理的设计原则,并提供了能够为生物技术应用解码复杂信号的原始合成系统。