Department of Physics, Sapienza University of Rome, Roma, Italy; Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Rome, Italy
Department of Physics, Sapienza University of Rome, Roma, Italy; Center for Life Nano & Neuro Science, Fondazione Istituto Italiano di Tecnologia (IIT), Roma, Italy
Department of Physics, Sapienza University of Rome, Roma, Italy; NANOTEC-CNR, Soft and Living Matter Laboratory, Institute of Nanotechnology, Rome, Italy
Department of Physics, Sapienza University of Rome, Roma, Italy; NANOTEC-CNR, Soft and Living Matter Laboratory, Institute of Nanotechnology, Rome, Italy
Department of Physics, Sapienza University of Rome, Roma, Italy; NANOTEC-CNR, Soft and Living Matter Laboratory, Institute of Nanotechnology, Rome, Italy
Synthetic genetic oscillators can serve as internal clocks within engineered cells to program periodic expression. However, cell-to-cell variability introduces a dispersion in the characteristics of these clocks that drives the population to complete desynchronization. Here, we introduce the optorepressilator, an optically controllable genetic clock that combines the repressilator, a three-node synthetic network in E. coli, with an optogenetic module enabling to reset, delay, or advance its phase using optical inputs. We demonstrate that a population of optorepressilators can be synchronized by transient green light exposure or entrained to oscillate indefinitely by a train of short pulses, through a mechanism reminiscent of natural circadian clocks. Furthermore, we investigate the system’s response to detuned external stimuli observing multiple regimes of global synchronization. Integrating experiments and mathematical modeling, we show that the entrainment mechanism is robust and can be understood quantitatively from single cell to population level.
