Real-time control of a genetic toggle switch

Recent progresses in microfluidics, synthetic biology, and microscopy automation now make it possible to control gene expression externally and in real time. Among the challenges facing the field of external real-time control of gene expression is the control of intricate, multistable gene regulation networks as well as the control of several target genes at the same time. To advance the domain in this direction, I studied the controllability of a simple bistable two-genes network, the so-called genetic toggle switch, in the vicinity of its unstable equilibrium point for extended periods of time. In this talk, I will present the development of a custom control platform for external control of gene expression at the single-cell level as well as a bacterial cellular chassis and a library of toggle switch genetic circuits. This platform is used to drive and maintain the genetic toggle switch in its region of instability with both closed-loop and open-loop strategies, for single cells and for populations of cells. Finally, both experimental and theoretical results demonstrate the emergence of new regimes of stability in gene regulation networks when submitted to oscillating chemical environments because of dynamic stabilization phenomenons, and can bring new insights to the study of cellular decision-making.