A load driver device for engineering modularity in biological networks
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Author(s)
Mishra, Deepak
Lin, Allen
Del Vecchio, Domitilla
Weiss, Ron
Rivera, Phillip M.
Date Issued
November 2014
Journal
Nature Biotechnology
Publisher
Nature Publishing Group
Citation
Mishra, Deepak, Phillip M Rivera, Allen Lin, Domitilla Del Vecchio, and Ron Weiss. “A Load Driver Device for Engineering Modularity in Biological Networks.” Nature Biotechnology 32, no. 12 (November 24, 2014): 1268–1275.
Version
Author's final manuscript
Abstract
The behavior of gene modules in complex synthetic circuits is often unpredictable. After joining modules to create a circuit, downstream elements (such as binding sites for a regulatory protein) apply a load to upstream modules that can negatively affect circuit function. Here we devised a genetic device named a load driver that mitigates the impact of load on circuit function, and we demonstrate its behavior in Saccharomyces cerevisiae. The load driver implements the design principle of timescale separation: inclusion of the load driver's fast phosphotransfer processes restores the capability of a slower transcriptional circuit to respond to time-varying input signals even in the presence of substantial load. Without the load driver, we observed circuit behavior that suffered from a 76% delay in response time and a 25% decrease in system bandwidth due to load. With the addition of a load driver, circuit performance was almost completely restored. Load drivers will serve as fundamental building blocks in the creation of complex, higher-level genetic circuits.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Massachusetts Institute of Technology. Department of Mechanical Engineering
Massachusetts Institute of Technology. Synthetic Biology Center
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DOI of Published Version
https://doi.org/10.1038/nbt.3044
