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Towards real-time control of gene expression: in silico analysis

One major goal of systems biology is to understand the dynamical functioning of biological systems at the cellular level. A common approach to investigate the dynamics of a system is to observe its response to perturbations. To improve our capacity to perturb cellular processes via the expression of a given protein with a chosen temporal expression profile, we develop an experimental platform for the real time control of gene expression.

In short, this platform allows for applying short osmotic stresses to yeast cells, that trigger the expression of a target gene via the activation of the HOG signal transduction pathway, and for observing in real time the cellular response. In Uhlendorf et al. (PSB'11), we describe preliminary experimental results on the control of the signal transduction pathway obtained using a simple proportional-integral controller. However, the control of the full system, including the much slower transcription and translation processes, necessitates more elaborate control methods.

Here, we propose a cascaded model-based control strategy tailored to the specificities of the biological system, notably to its perfect adaptation to osmotic stress. The receding horizon control problems are then iteratively solved using global optimization tools. The practical feasibility and the robustness of the proposed approach with respect to gene expression noise is tested in silico using a simple, switched linear model of the osmostress response in yeast.

Joint work with Jannis Uhlendorf (INRIA/MSC) and Pascal Hersen (MSC).

Type of Seminar:
IfA BISON Seminar
Dr. Gregory Batt
INRIA, Rocquencourt, France
Oct 11, 2011   13:30

Contact Person:

Elias August
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