To refer to this page use:
|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-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 FOS, elucidating how the BTG2 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.|
|Citation:||Ravindran, Pavithran T, Wilson, Maxwell Z, Jena, Siddhartha G, Toettcher, Jared E. (2020). Engineering combinatorial and dynamic decoders using synthetic immediate-early genes. Communications biology, 3 (1), 436 - 436. doi:10.1038/s42003-020-01171-1|
|Pages:||436 - 436|
|Type of Material:||Journal Article|
|Journal/Proceeding Title:||Communications Biology|
|Version:||Final published version. This is an open access article.|
Items in OAR@Princeton are protected by copyright, with all rights reserved, unless otherwise indicated.