title: A load driver device for engineering modularity in biological networks.
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.
authors.affiliation: 1] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Mishra
authors.affiliation: 1] Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Phillip M
authors.identifier: 0000000213404915
authors.initials: PM
authors.lastname: Rivera
authors.affiliation: 1] Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] Department of Electrical Engineering/Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Allen
authors.initials: A
authors.lastname: Lin
authors.affiliation: 1] Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Domitilla
authors.initials: D
authors.lastname: Del Vecchio
authors.affiliation: 1] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Department of Electrical Engineering/Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Weiss
mesh_terms: D001665:Binding Sites; D053263:Gene Regulatory Networks; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D012045:Regulatory Sequences, Nucleic Acid; D012441:Saccharomyces cerevisiae / Q000235:genetics