A load driver device for engineering modularity in biological networks

Nat Biotechnol. 2014 Dec;32(12):1268-75. doi: 10.1038/nbt.3044. Epub 2014 Nov 24.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Gene Regulatory Networks*
  • Models, Theoretical*
  • Molecular Sequence Data
  • Regulatory Sequences, Nucleic Acid
  • Saccharomyces cerevisiae / genetics

Associated data

  • GENBANK/KM457485
  • GENBANK/KM457486
  • GENBANK/KM457487
  • GENBANK/KM457488
  • GENBANK/KM457489
  • GENBANK/KM457490