Modeling and Mitigating Molecular Loads for Genetic Circuit Engineering

Abstract

Genetic circuits control every aspect of life and thus the ability to engineer them de-novo opens exciting possibilities, from revolutionary drugs and green energy to bugs that recognize and kill cancer cells. Just like in mechanical, electrical, and hydraulic systems, the problem of loading, or back-action, is encountered when engineering genetic circuits. These molecular loads can be severe to the point of completely destroying the intended function of a circuit. In this talk, I will review a systems theoretic modeling formalism, grounded on the concept of retroactivity, that captures molecular loads in a way that makes the loading problem amenable of a solution. I will, in particular, focus on two types of loading: inter-module loads and loads to cellular resources that feed the modules. I will show experimentally validated models of loading effects on the emergent dynamics of a system and nonlinear control techniques that we have developed and implemented to mitigate these effects.