Growth feedback confers cooperativity in resource-competing synthetic gene circuits

Melendez-Alvarez, Juan; Zhang, Rong; Tian, Xiao‐Jun

doi:10.1016/j.chaos.2023.113713

Cited by 3 publications

(4 citation statements)

References 39 publications

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“…( 7 ): A Hill relationship akin to Eq. ( 7 ) is sometimes used in resource-aware models that abstract the host’s native gene expression yet aim to capture cell growth rate’s burden-dependence 17 , 18 . However, these relations involve scaling factors defined arbitrarily for each synthetic circuit, such as the “metabolic burden threshold” in ref.…”

Section: Resultsmentioning

confidence: 99%

“…However, these relations involve scaling factors defined arbitrarily for each synthetic circuit, such as the “metabolic burden threshold” in ref. 18 . Conversely, our expression only involves the physiological parameters of native and synthetic genes.…”

Section: Resultsmentioning

confidence: 99%

“…One approach exclusively considers synthetic genes, applying effective rate frameworks to obtain a simple, easily interpretable model that predicts a circuit’s behavior and the impact of changing its design parameters 6 , 9 , 12 . In this case, the interplay between heterologous gene expression and the host cell’s state is either neglected 12 or abstracted and captured by simple phenomenological relations, which involve circuit-specific parameters without clear physiological meaning and do not mechanistically explain the effects of burden 18 . On the other hand, models of the entire bacterial cell reveal how resources are allocated between the host’s own genes and those of the synthetic circuit 28 , 38 .…”

Section: Discussionmentioning

confidence: 99%

“…Bacterial cells are fast-growing, so dilution due to cell division significantly influences gene expression dynamics 16 . Accordingly, changes in the cell’s growth rate caused by gene expression burden can qualitatively alter a gene circuit’s behavior 16 – 18 . Moreover, the size of a bacterial cell’s pool of gene expression machinery—specifically, ribosomes—is also related to its growth rate 19 , 20 .…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Sechkar,

Steel,

Perrino

et al. 2024

Nat Commun

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Sechkar,

Steel,

Perrino

et al. 2024

Nat Commun

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Context-dependent redesign of robust synthetic gene circuits

Stone,

Youssef,

Rijal

et al. 2024

Trends in Biotechnology

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Noise Reduction in Resource-Coupled Multi-Module Gene Circuits through Antithetic Feedback Control

Chakravarty,

Zhang,

Tian

2024

Preprint

Self Cite

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Gene circuits within the same host cell often experience coupling, stemming from the competition for limited resources during transcriptional and translational processes. This resource competition introduces an additional layer of noise to gene expression. Here we present three multi-module antithetic control strategies: negatively competitive regulation (NCR) controller, alongside local and global controllers, aimed at reducing the gene expression noise within the context of resource competition. Through stochastic simulations and fluctuation-dissipation theorem (FDT) analysis, our findings highlight the superior performance of the NCR antithetic controller in reducing noise levels. Our research provides an effective control strategy for attenuating resource-driven noise and offers insight into the development of robust gene circuits.

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Growth feedback confers cooperativity in resource-competing synthetic gene circuits

Cited by 3 publications

References 39 publications

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

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

Context-dependent redesign of robust synthetic gene circuits

Noise Reduction in Resource-Coupled Multi-Module Gene Circuits through Antithetic Feedback Control

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