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Engineering combinatorial and dynamic decoders using synthetic immediate-early genes

Author(s): Ravindran, Pavithran T; Wilson, Maxwell Z; Jena, Siddhartha G; Toettcher, Jared E

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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.
Publication Date: 13-Aug-2020
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
DOI: doi:10.1038/s42003-020-01171-1
ISSN: 2399-3642
EISSN: 2399-3642
Pages: 436 - 436
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: Communications Biology
Version: Final published version. This is an open access article.

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