Embedded control of cell growth using tunable genetic systems

Fusco,; Salzano, Davide; Fiore, Davide; Bernardo, Mario di

doi:10.1002/rnc.5982

“…Indeed, several solutions have been proposed in the literature in this direction, such as the antithetic feedback controller guaranteeing robust perfect adaptation in noisy biomolecular networks [5], [6], or the implementation via biological molecules in a single cell of a proportionalintegral-derivative control strategy [7]. Further examples of synthetic feedback mechanisms embedded in single cells can be found in [8], [9].…”

Section: Introductionmentioning

confidence: 99%

Multicellular PI Control for Gene Regulation in Microbial Consortia

Martinelli

¹

,

Salzano

²

,

Fiore

³

et al. 2022

IEEE Control Syst. Lett.

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We describe two multicellular implementations of the classical P and PI feedback controllers for the regulation of gene expression in a target cell population. Specifically, we propose to distribute the proportional and integral actions over two different cellular populations in a microbial consortium comprising a third target population whose output needs to be regulated. By engineering communication among the different cellular populations via appropriate orthogonal quorum sensing molecules, we are able to close the feedback loop across the consortium. We derive analytical conditions on the biological parameters guaranteeing the regulation of the output of the target population and we validate the robustness and modularity of proposed control schemes via in silico experiments in BSim, a realistic agent-based simulator of bacterial populations.

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“…Different solutions to regulate the relative size of coexisting cell populations have been proposed in the literature, mostly based on embedding additional genetic circuitry in the cells that make them able to sense and respond to each other's relative size [13][14][15][16][17][18]. Specifically, by sensing the density of the other group, cells can either increase their growth rate by producing some growth regulator protein (e.g.…”

Section: Introductionmentioning

confidence: 99%

Ratiometric control of cell phenotypes in monostrain microbial consortia

Salzano

¹

,

Fiore

²

,

Bernardo

³

2022

J. R. Soc. Interface.

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We address the problem of regulating and keeping at a desired balance the relative numbers between cells exhibiting a different phenotype within a monostrain microbial consortium. We propose a strategy based on the use of external control inputs, assuming each cell in the community is endowed with a reversible, bistable memory mechanism. Specifically, we provide a general analytical framework to guide the design of external feedback control strategies aimed at balancing the ratio between cells whose memory is stabilized at either one of two equilibria associated with different cell phenotypes. We demonstrate the stability and robustness properties of the control laws proposed and validate them in silico , implementing the memory element via a genetic toggle-switch. The proposed control framework may be used to allow long-term coexistence of different populations, with both industrial and biotechnological applications. As a representative example, we consider the realistic agent-based implementation of our control strategy to enable cooperative bioproduction of a dimer in a monostrain microbial consortium.

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“…Indeed, several solutions have been proposed in the literature in this direction, such as the antithetic feedback controller guaranteeing robust perfect adaptation in noisy biomolecular networks [5], [6], or the implementation via biological molecules in a single cell of a proportional-integral-derivative control strategy [7]. Further examples of synthetic feedback mechanisms embedded in single cells can be found in [8], [9].…”

Section: Introductionmentioning

confidence: 99%

Multicellular PI control for gene regulation in microbial consortia

Martinelli

¹

,

Salzano

²

,

Fiore

³

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

We describe two multicellular implementations of the classical P and PI feedback controllers for the regulation of gene expression in a target cell population. Specifically, we propose to distribute the proportional and integral actions over two different cellular populations in a microbial consortium comprising a third target population whose output needs to be regulated. By engineering communication among the different cellular populations via appropriate orthogonal quorum sensing molecules, we are able to close the feedback loop across the consortium. We derive analytical conditions on the biological parameters guaranteeing the regulation of the output of the target population and we validate the robustness and modularity of proposed control schemes via in silico experiments in BSim, a realistic agent-based simulator of bacterial populations.

show abstract

Embedded control of cell growth using tunable genetic systems

Cited by 3 publications

References 51 publications

Multicellular PI Control for Gene Regulation in Microbial Consortia

Multicellular PI Control for Gene Regulation in Microbial Consortia

Ratiometric control of cell phenotypes in monostrain microbial consortia

Multicellular PI control for gene regulation in microbial consortia

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