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A load driver device for engineering modularity in biological networks

Author(s)
Mishra, Deepak; Lin, Allen; Del Vecchio, Domitilla; Weiss, Ron; Rivera, Phillip M.
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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.
Date issued
2014-11
URI
http://hdl.handle.net/1721.1/97410
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
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
ISSN
1087-0156
1546-1696

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