Performance and robustness analysis of control strategies for ameliorating cellular host-circuit interactions

Recent work on engineering synthetic cellular circuitry has shown that non-regulatory interactions brought about through competition for shared gene expression re-sources, such as ribosomes, can result in degraded performance (where circuit behaviour deviates from design specifications) or even failure (qualitatively different functionality). Numerous feedback control strategies have been proposed to decouple co-expressed genes in simple genetic circuits; ranging from feedback within the circuit, resource allocation schemes and growth-based feedback. In this work, we utilise a whole cell mathematical model, which captures key gene expression trade-offs, to compare these control strategies for their ability to ame-liorate the impact of resource limitations, maintain growth and assess their robustness to host uncertainty and environmental variation.