Retroactivity attenuation in transcriptional networks: Design and analysis of an insulation device

Retroactivity is a phenomenon that changes the desired input/output response of a system when it is connected to “downstream” systems. Transcriptional networks are not immune to this phenomenon. In this paper, we propose a phosphorylation-based design for a bio-molecular system that acts as an insulator between its upstream systems and its downstream ones in a transcriptional network. Performing singular perturbation analysis, we mathematically show that such a design attenuates retroactivity. Stochastic simulations are run to analyze the robustness of the proposed device to biological noise and to highlight design tradeoffs.