A synthetic gene circuit for imaging-free detection of signaling pulses.

ABSTRACT: Cells employ intracellular signaling pathways to sense and respond to changes in their external environment. In recent years, live-cell biosensors have revealed complex pulsatile dynamics in many pathways, but studies of these signaling dynamics are limited by the necessity of live-cell imaging at high spatiotemporal resolution. Here, we describe an approach to infer pulsatile signaling dynamics from a single measurement in fixed cells using a pulse-detecting gene circuit. We computationally screened for circuits with the capability to selectively detect signaling pulses, revealing an incoherent feedforward topology that robustly performs this computation. We implemented the motif experimentally for the Erk signaling pathway using a single engineered transcription factor and fluorescent pr

SUBMITTER: Ravindran PT 

PROVIDER: S-EPMC8857027 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature