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Using single-cell models to predict the functionality of synthetic circuits at the population scale

Abstract : Mathematical modeling has become a major tool to guide the characterization and synthetic construction of cellular processes. However, models typically lose their capacity to explain or predict experimental outcomes as soon as any, even minor, modification of the studied system or its operating conditions is implemented. This limits our capacity to fully comprehend the functioning of natural biological processes and is a major roadblock for the de novo design of complex synthetic circuits. Here, using a specifically constructed yeast optogenetic differentiation system as an example, we show that a simple deterministic model can explain system dynamics in given conditions but loses validity when modifications to the system are made. On the other hand, deploying theory from stochastic chemical kinetics and developing models of the system’s components that simultaneously track single-cell and population processes allows us to quantitatively predict emerging dynamics of the system without any adjustment of model parameters. We conclude that carefully characterizing the dynamics of cell-to-cell variability using appropriate modeling theory may allow one to unravel the complex interplay of stochastic single-cell and population processes and to predict the functionality of composed synthetic circuits in growing populations before the circuit is constructed.
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Preprints, Working Papers, ...
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https://hal.inria.fr/hal-03544044
Contributor : Gregory Batt Connect in order to contact the contributor
Submitted on : Friday, January 28, 2022 - 10:52:54 AM
Last modification on : Monday, April 11, 2022 - 4:54:02 PM
Long-term archiving on: : Friday, April 29, 2022 - 6:30:10 PM

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2021.08.03.454887v1.full.pdf
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Distributed under a Creative Commons Attribution 4.0 International License

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Chetan Aditya, François Bertaux, Gregory Batt, Jakob Ruess. Using single-cell models to predict the functionality of synthetic circuits at the population scale. 2021. ⟨hal-03544044⟩

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