Control Group and OHMC Seminar: Maurice Filo, ETH Zurich

Speaker: Maurice Filo, ETH Zurich

Title: Engineering Genetic Controllers to Accelerate Adaptation and Attenuate Cellular Noise

Abstract: Cells excel at regulating internal processes with speed, precision, and resilience. Inspired by this, synthetic biology increasingly employs feedback control to engineer robust, adaptive behaviors. Yet, molecular noise, saturation, nonlinearities, and structural constraints pose major design challenges. This talk explores molecular feedback controllers that achieve Robust Perfect Adaptation (RPA)—maintaining steady-state output despite persistent disturbances—while improving dynamic response and suppressing intrinsic noise.

We begin with the Antithetic Integral Feedback (AIF) motif, a chemical reaction network (CRN) implementing integral control, and extend it to nonlinear architectures that emulate PID control through biologically feasible feedback circuits. These designs respect strict CRN constraints, introducing unique synthesis and analysis challenges. I also briefly touch on anti-windup strategies that mitigate performance degradation under saturation.

Next, we examine simpler architectures that exploit nonlinearities to realize PI control with minimal complexity—an especially valuable trait for practical implementation in synthetic biology. Despite their simplicity, these controllers deliver RPA, high dynamic performance, and intrinsic noise suppression. I present theoretical results showing these minimal designs outperform standard negative feedback loops, even under non-ideal conditions. Building on these insights, we outline practical guidelines for modifying negative feedback circuits, built with genetic repressors, to improve disturbance rejection, dynamic response, and noise suppression. Finally, I present an experimental implementation using inteins, protein elements that catalyze splicing. The strong alignment between theory and experiment underscores a robust, versatile framework for synthetic feedback control, with applications from therapeutic systems to advanced biotechnologies.

Bio: Maurice Filo earned his diploma in electrical engineering from the Lebanese University in Beirut, Lebanon, followed by an M.Sc. from the American University of Beirut. He then obtained a second M.Sc. and a Ph.D. in mechanical engineering from the University of California, Santa Barbara (UCSB). During his time at UCSB, Maurice was awarded the Outstanding Scholar Fellowship from the Center for Control, Dynamical-systems, and Computation (CCDC) and the Holbrook Foundation Fellowship from the Institute for Energy Efficiency (IEE). He also received the Best Ph.D. Thesis Award from the CCDC. Following his Ph.D., Maurice joined ETH Zurich as a postdoctoral researcher before becoming a senior research scientist. His research currently focuses on control theory in synthetic biology, where he develops theoretical and computational tools for designing and analyzing robust biological control systems. One of his patents was ranked among the top 20 inventions at the Spark Award at ETH Zurich.

We strongly encourage you to attend the seminar in person.

You can also connect via Zoom: https://newnham.zoom.us/j/92544958528?pwd=YS9PcGRnbXBOcStBdStNb3E0SHN1UT09