Toward Systems Biology

May 30 - 31, June 1, 2011


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Towards Real-Time Control of Gene Expression

To cope with the complexity of biological systems, quantitative experimental approaches and quantitative models are increasingly used. Obtaining a quantitative description of biological processes necessitates the capability to observe the response of biological systems subjected to large numbers of different perturbations. However, because of the difficulty to perturb precisely a biological system in a dynamical manner, most studies simply use step-response, static perturbations. In contrast, time-varying perturbations have the capacity to provide much richer information on the system dynamics. To improve our capacity to express in vivo a protein of interest in a chosen time-dependant way, and thus perturb biological systems, we propose to develop a platform for the real-time control of gene expression.

The platform integrates a microfluidic device that allows modulating gene expression by changing the extracellular environment, a fluorescent microscope that allows monitoring gene expression, and computational approaches that in real time compute the inputs to apply to the system to obtain the desired outputs. In this work, we present preliminary results on the control of the nuclear localization of the osmoresponsive transcription factor Hog1 in yeast using our platform equipped with a simple PID controller, and on the development more elaborate, model-based control approaches.

Gregory Batt, INRIA Paris-Rocquencourt

Joint work with Jannis Uhlendorf (INRIA Paris-Rocquencourt & MSC Lab CNRS/Paris Diderot U) and Pascal Hersen (MSC Lab CNRS/Paris Diderot U)