Integral Control Feedback Circuit for the Reactivation of Malfunctioning p53 Pathway

TL;DR

This paper presents a synthetic integral feedback control circuit designed to regulate p53 protein levels, ensuring stability and robustness in the p53 pathway through a mathematical model incorporating microRNA regulation.

Contribution

It introduces a novel synthetic circuit with integral feedback control based on a p53-MDM2-miRNA model to restore p53 levels when they fall below a threshold.

Findings

The control circuit effectively stabilizes p53 levels against perturbations.

Different circuit architectures show varying degrees of adaptive response.

The approach demonstrates potential for therapeutic regulation of p53.

Abstract

We developed a strategy to control p53 levels when the p53 concentration falls below a desired threshold . Based on an established p53-MDM2 mathematical model that also incorporates microRNA regulators (p53-MDM2-miRNA), we applied a control action in closed-loop with respect to this model. In particular, we employ various architectures of synthetic circuit with integral feedback control, illustrating varying degree in adaptive response to step-wise perturbation of p53.