@article{178141,
  author = {PT Ravindran and MZ Wilson and SG Jena and JE Toettcher},
  title = {Engineering combinatorial and dynamic decoders using synthetic immediate-early genes},
  abstract = { Many cell- and tissue-level functions are coordinated by intracellular signaling pathways that trigger the expression of context-specific target genes. Yet the input{\textendash}output relationships that link pathways to the genes they activate are incompletely understood. Mapping the pathway-decoding logic of natural target genes could also provide a basis for engineering novel signal-decoding circuits. Here we report the construction of synthetic immediate-early genes (SynIEGs), target genes of Erk signaling that implement complex, user-defined regulation and can be monitored by using live-cell biosensors to track their transcription and translation. We demonstrate the power of this approach by confirming Erk duration-sensing by~<i>FOS</i>, elucidating how the~<i>BTG2</i>~gene is differentially regulated by external stimuli, and designing a synthetic immediate-early gene that selectively responds to the combination of growth factor and DNA damage stimuli. SynIEGs pave the way toward engineering molecular circuits that decode signaling dynamics and combinations across a broad range of cellular contexts. },
  year = {2020},
  journal = {Commun Biol},
  url = {https://www.nature.com/articles/s42003-020-01171-1},
  language = {eng},
}