Towards real-time control of gene expression: controlling the HOG signaling cascade.

To decipher the dynamical functioning of cellular processes, the method of choice is to observe the time response of cells subjected to well controlled perturbations in time and amplitude. Efficient methods, based on molecular biology, are available to monitor quantitatively and dynamically many cellular processes. In contrast, it is still a challenge to perturb cellular processes - such as gene expression - in a precise and controlled manner. Here, we propose a first step towards in vivo control of gene expression: in real-time, we dynamically control the activity of a yeast signaling cascade thanks to an experimental platform combining a micro-fluidic device, an epi-fluorescence microscope and software implementing control approaches. We experimentally demonstrate the feasibility of this approach, and we investigate computationally some possible improvements of our control strategy using a model of the yeast osmo-adaptation response fitted to our data.