title: In silico control of biomolecular processes.
abstract: By implementing an external feedback loop one can tightly control the expression of a gene over many cell generations with quantitative accuracy. Controlling precisely the level of a protein of interest will be useful to probe quantitatively the dynamical properties of cellular processes and to drive complex, synthetically-engineered networks. In this chapter we describe a platform for real-time closed-loop control of gene expression in yeast that integrates microscopy for monitoring gene expression at the cell level, microfluidics to manipulate the cells environment, and original software for automated imaging, quantification, and model predictive control. By using an endogenous osmo-stress responsive promoter and playing with the osmolarity of the cells environment, we demonstrate that long-term control can indeed be achieved for both time-constant and time-varying target profiles, at the population level, and even at the single-cell level.
authors.affiliation: INRIA Paris-Rocquencourt, Domaine de Voluceau, Rocquencourt - BP 105, 78153, Le Chesnay, France.
authors.forename: Jannis
authors.initials: J
authors.lastname: Uhlendorf
authors.forename: Agnès
authors.initials: A
authors.lastname: Miermont
authors.forename: Thierry
authors.initials: T
authors.lastname: Delaveau
authors.forename: Gilles
authors.initials: G
authors.lastname: Charvin
authors.forename: François
authors.initials: F
authors.lastname: Fages
authors.forename: Samuel
authors.initials: S
authors.lastname: Bottani
authors.forename: Pascal
authors.initials: P
authors.lastname: Hersen
authors.forename: Gregory
authors.initials: G
authors.lastname: Batt
mesh_terms: D012984:Software; D049490:Systems Biology / Q000379:methods*