Abstract

Feedback regulation is one of the most fundamental principles in biology, from the homeostasis that regulates our body temperature down to the molecular control mechanisms that ensure that each cell on Earth is producing all of the right proteins and other biological molecules at the right time in order to survive in an uncertain world. Given the many examples of biological feedback control given to us by evolution, it is somewhat surprising how difficult it still is for us humans to successfully engineer feedback regulation in synthetic biological circuits.

In this talk, I will first discuss theoretical work that I carried out during my PhD where we attempted to translate some tools from control theory (using e.g., Bode’s Integral Theorem and some more recent results developed by Fulvio Forni and Rodolphe Sepulchre on dominance analysis) into the domain of biology, specifically focusing on a novel class of engineered genetic control circuits called an antithetic integral feedback controller. Next, I will present ongoing work where we are developing novel experimental techniques that we hope will make it possible to actually use the theory to drive the design and analysis of real synthetic circuits acting in living bacterial cells. My goal is to illustrate through this example what I have learned about the gap between the types of tools we use in classical control contexts, and what it is that makes biology such a challenging domain of application for those tools.