Modelling genetic stability in engineered cell populations

Duncan Ingram and Guy-Bart Stan ()
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Duncan Ingram: Imperial College London
Guy-Bart Stan: Imperial College London

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract Predicting the evolution of engineered cell populations is a highly sought-after goal in biotechnology. While models of evolutionary dynamics are far from new, their application to synthetic systems is scarce where the vast combination of genetic parts and regulatory elements creates a unique challenge. To address this gap, we here-in present a framework that allows one to connect the DNA design of varied genetic devices with mutation spread in a growing cell population. Users can specify the functional parts of their system and the degree of mutation heterogeneity to explore, after which our model generates host-aware transition dynamics between different mutation phenotypes over time. We show how our framework can be used to generate insightful hypotheses across broad applications, from how a device’s components can be tweaked to optimise long-term protein yield and genetic shelf life, to generating new design paradigms for gene regulatory networks that improve their functionality.

Date: 2023
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DOI: 10.1038/s41467-023-38850-6

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