Gregory Batt (INRIA, Saclay). Biophysics seminar ESPCI-ENS.

10 February 2017 13:00 » 14:00 — ESPCI, Amphi Urbain, Ground Floor, Staircase N

Balancing a genetic toggle switch by real-time control or periodic stimulations

The ability to routinely control complex genetic circuits in vivo and in real-time promises quantitative understanding of cellular processes of unprecedented precision, quality, and richness. With combined efforts in microfluidic design, microscope automation, image
segmentation and analysis, and control theory, we propose a platform for real-time, single-cell, in silico control and monitoring of genetic networks in E. coli. The circuits we are trying to control are based on the genetic toggle switch, a foundational circuit in
synthetic biology, which consists of two genes that repress each other. This genetic system features two stable equilibrium points where one of the genes has taken over. Our objective is to dynamically balance the circuit in single cells around a third, unstable
equilibrium point at which no gene dominates and their mutual repression strengths are balanced. This is similar to the landmark problem in control theory of stabilizing a pendulum in its upright position (inverted pendulum). We show that even a simple
Proportional-Integral controller can drive the toggle switch to a desired set point and demonstrate that obtaining a state of balanced expression is even possible with a periodic dynamic input. Surprisingly, cellular heterogeneity does not prevent us from
obtaining balanced expression in all cells in the population.