Gene networks that compensate for crosstalk with crosstalk
Name
s41467-019-12021-y.pdf
Description
Published version
Size
703.92 KB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Müller, Isaak E.
Rubens, Jacob R.
Jun, Tomi
Xavier, Ramnik
Lu, Timothy K.
Date Issued
September 6, 2019
Journal
Nature communications
Publisher
Springer Science and Business Media LLC
Citation
Müller, Isaak E. et al. "Gene networks that compensate for crosstalk with crosstalk." Nature communications 10 (2019): 1038 © 2019 The Author(s)
Version
Final published version
Abstract
Crosstalk is a major challenge to engineering sophisticated synthetic gene networks. A common approach is to insulate signal-transduction pathways by minimizing molecular-level crosstalk between endogenous and synthetic genetic components, but this strategy can be difficult to apply in the context of complex, natural gene networks and unknown interactions. Here, we show that synthetic gene networks can be engineered to compensate for crosstalk by integrating pathway signals, rather than by pathway insulation. We demonstrate this principle using reactive oxygen species (ROS)-responsive gene circuits in Escherichia coli that exhibit concentration-dependent crosstalk with non-cognate ROS. We quantitatively map the degree of crosstalk and design gene circuits that introduce compensatory crosstalk at the gene network level. The resulting gene network exhibits reduced crosstalk in the sensing of the two different ROS. Our results suggest that simple network motifs that compensate for pathway crosstalk can be used by biological networks to accurately interpret environmental signals.
Subjects
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy
General Chemistry
MIT Department
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Massachusetts Institute of Technology. Microbiology Graduate Program
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/s41467-019-12021-y
