A quasi-integral controller for adaptation of genetic modules to variable ribosome demand
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s41467-018-07899-z.pdf
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1.26 MB
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Adobe PDF
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604577643078017a1bbbbf1e64ec64ab
Author(s)
Huang, Hsin-Ho
Qian, Yili
Del Vecchio, Domitilla
Date Issued
December 2018
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Huang, Hsin-Ho, Yili Qian, and Domitilla Del Vecchio. “A Quasi-Integral Controller for Adaptation of Genetic Modules to Variable Ribosome Demand.” Nature Communications 9, no. 1 (December 2018).
Version
Final published version
Abstract
The behavior of genetic circuits is often poorly predictable. A gene’s expression level is not only determined by the intended regulators, but also affected by changes in ribosome availability imparted by expression of other genes. Here we design a quasi-integral biomolecular feedback controller that enables the expression level of any gene of interest (GOI) to adapt to changes in available ribosomes. The feedback is implemented through a synthetic small RNA (sRNA) that silences the GOI’s mRNA, and uses orthogonal extracytoplasmic function (ECF) sigma factor to sense the GOI’s translation and to actuate sRNA transcription. Without the controller, the expression level of the GOI is reduced by 50% when a resource competitor is activated. With the controller, by contrast, gene expression level is practically unaffected by the competitor. This feedback controller allows adaptation of genetic modules to variable ribosome demand and thus aids modular construction of complicated circuits.
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/s41467-018-07899-z
