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Real-time control of a genetic toggle switch

Abstract : 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 we 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. Throughout this document, we 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 for us to control. We use the platform to drive and maintain our genetic system in its region of unstability with both closed-loop and open-loop strategies. Not only do we demonstrate that in silico control platforms can control genetic systems in out-of-equilibrium states, we also notably maintain a population of cells in their unstable area with open-loop periodic stimulations. These results suggest the possible emergence of different regimes of stability in gene regulation networks submitted to fluctuating environments, and can potential insights in the study of cellular decision making. We also introduce a new approach for microscopy image analysis which exploits information hidden in several focal planes around the specimen instead of using only a single-plane image. The objective of this method is to automatically label different parts of an image with machine learning techniques inspired by hyperspectral imaging. The method is then shown to facilitate segmentation and be easily adaptable to various different organisms
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https://tel.archives-ouvertes.fr/tel-01417700
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Submitted on : Monday, June 25, 2018 - 6:40:14 PM
Last modification on : Saturday, July 11, 2020 - 4:45:22 AM
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  • HAL Id : tel-01417700, version 2

Citation

Jean-Baptiste Lugagne. Real-time control of a genetic toggle switch. Biological Physics [physics.bio-ph]. Université Sorbonne Paris Cité, 2016. English. ⟨NNT : 2016USPCC249⟩. ⟨tel-01417700v2⟩

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