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A coarse-grained bacterial cell model for resource-aware analysis and design of synthetic gene circuits

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Title: A coarse-grained bacterial cell model for resource-aware analysis and design of synthetic gene circuits
Authors: Sechkar, K
Harrison, S
Perrino, G
Stan, G-B
Stan, G-B
Item Type: Journal Article
Abstract: Within a cell, synthetic and native genes compete for expression machinery, influencing cellular process dynamics through resource couplings. Models that simplify competitive resource binding kinetics can guide the design of strategies for countering these couplings. However, in bacteria resource availability and cell growth rate are interlinked, which complicates resource-aware biocircuit design. Capturing this interdependence requires coarse-grained bacterial cell models that balance accurate representation of metabolic regulation against simplicity and interpretability. We propose a coarse-grained E. coli cell model that combines the ease of simplified resource coupling analysis with appreciation of bacterial growth regulation mechanisms and the processes relevant for biocircuit design. Reliably capturing known growth phenomena, it provides a unifying explanation to disparate empirical relations between growth and synthetic gene expression. Considering a biomolecular controller that makes cell-wide ribosome availability robust to perturbations, we showcase our model’s usefulness in numerically prototyping biocircuits and deriving analytical relations for design guidance.
Issue Date: 4-Mar-2024
Date of Acceptance: 27-Feb-2024
URI: http://hdl.handle.net/10044/1/110520
DOI: 10.1038/s41467-024-46410-9
ISSN: 2041-1723
Publisher: Springer Nature
Journal / Book Title: Nature Communications
Volume: 15
Copyright Statement: © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Publication Status: Published
Article Number: 1981
Online Publication Date: 2024-03-04
Appears in Collections:Bioengineering



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