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SUMMARY:Engineering Genetic Controllers to Accelerate Adaptation and Atten
 uate Cellular Noise - Maurice Filo\, ETH Zurich
DTSTART:20250522T130000Z
DTEND:20250522T140000Z
UID:TALK232525@talks.cam.ac.uk
CONTACT:Fulvio Forni
DESCRIPTION:Cells excel at regulating internal processes with speed\, prec
 ision\, and resilience. Inspired by this\, synthetic biology increasingly 
 employs feedback control to engineer robust\, adaptive behaviors. Yet\, mo
 lecular noise\, saturation\, nonlinearities\, and structural constraints p
 ose major design challenges. This talk explores molecular feedback control
 lers that achieve Robust Perfect Adaptation (RPA)—maintaining steady-sta
 te output despite persistent disturbances—while improving dynamic respon
 se and suppressing intrinsic noise.\n\nWe begin with the Antithetic Integr
 al Feedback (AIF) motif\, a chemical reaction network (CRN) implementing i
 ntegral control\, and extend it to nonlinear architectures that emulate PI
 D control through biologically feasible feedback circuits. These designs r
 espect strict CRN constraints\, introducing unique synthesis and analysis 
 challenges. I also briefly touch on anti-windup strategies that mitigate p
 erformance degradation under saturation.\n\nNext\, we examine simpler arch
 itectures that exploit nonlinearities to realize PI control with minimal c
 omplexity—an especially valuable trait for practical implementation in s
 ynthetic biology. Despite their simplicity\, these controllers deliver RPA
 \, high dynamic performance\, and intrinsic noise suppression. I present t
 heoretical results showing these minimal designs outperform standard negat
 ive feedback loops\, even under non-ideal conditions. Building on these in
 sights\, we outline practical guidelines for modifying negative feedback c
 ircuits\, built with genetic repressors\, to improve disturbance rejection
 \, dynamic response\, and noise suppression. Finally\, I present an experi
 mental implementation using inteins\, protein elements that catalyze splic
 ing. The strong alignment between theory and experiment underscores a robu
 st\, versatile framework for synthetic feedback control\, with application
 s from therapeutic systems to advanced biotechnologies.\n\nThe seminar wil
 l be held in JDB Seminar Room\, Department of Engineering\, and online (zo
 om): https://newnham.zoom.us/j/92544958528?pwd=YS9PcGRnbXBOcStBdStNb3E0SHN
 1UT09
LOCATION:JDB Seminar Room\, Department of Engineering and online (Zoom)
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