Synthetic gene networks recapitulate dynamic signal decoding and differential gene expression

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. [Display omitted] •A synthetic incoherent feed-forward loop (IFFL) acts as a falling edge pulse detector•IFFL-based circuits enable demultiplexing and filtering of dynamic signals•Dynamic multiplexing increases information transmission capacity•Multiplexing enables input-dynamics-based differential regulation of metabolic genes Cells live in constantly changing environments and employ dynamic signaling pathways to transduce information. How cells decode dynamic signals and make use of the extracted information remains poorly understood. Using a synthetic biology approach, Benzinger et al. show that simple networks based on transcription factors with different response characteristics and gene regulatory interactions enable the processing and decoding of dynamic upstream signals.