Mitigation of resource competition in synthetic genetic circuits through feedback regulation

Abstract

A recurring challenge in the design of genetic circuits is context dependence, the fact that the behavior of a functional module is influenced by the state of the wider cellular milieu with which it interacts. One key player in context dependence is the scarcity of shared cellular resources, especially those required for transcription and translation during gene expression. Because of competition for these limited resources, the behavior of modules becomes coupled in subtle ways, preventing circuits from working as expected. This paper proposes a classical feedback control approach to mitigate the steady state effects of the competition for resources necessary for gene expression. In particular, we analyze and compare the ability of several inhibitory feedback regulation architectures to reduce the interdependence between different gene expression processes due to resource limitations.