Architectures for Combined Transcriptional and Translational Resource Allocation Controllers.

Darlington, Alexander P S; Bates, Declan G

Recent work on engineering synthetic cellular circuitry has shown that non-regulatory interactions mediated by competition for gene expression resources can result in degraded performance or even failure. Transcriptional and translational resource allocation controllers based on orthogonal circuit-specific gene expression machinery have separately been shown to improve modularity and circuit performance. Here, we investigate the potential advantages, challenges, and design trade-offs involved in combining transcriptional and translational controllers into a "dual resource allocation control system." We show that separately functional, translational, and transcriptional controllers cannot generally be combined without extensive redesign. We analyze candidate architectures for direct design of dual resource allocation controllers and propose modifications to improve their performance (in terms of decoupling and expression level) and robustness. We show that dual controllers can be built that are composed only of orthogonal gene expression resources and demonstrate that such designs offer both superior performance and robustness characteristics.