A load driver device for engineering modularity in biological networks

• Main Authors: Mishra, Deepak (Contributor), Lin, Allen (Contributor), Del Vecchio, Domitilla (Contributor), Weiss, Ron (Contributor), Rivera, Phillip M. (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science (Contributor), Massachusetts Institute of Technology. Department of Mechanical Engineering (Contributor), Massachusetts Institute of Technology. Synthetic Biology Center (Contributor)
• Format: Article
• Language: English
• Published: Nature Publishing Group, 2015-06-15T14:03:38Z.
• Subjects: Article
• Online Access: Get fulltext

 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.