Perfect adaptation in biology

Khammash, Mustafa

doi:10.1016/j.cels.2021.05.020

Cited by 91 publications

(88 citation statements)

References 56 publications

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“…In this section we provide descriptions of reaction networks in both deterministic and stochastic settings. Then we mathematically define our criterion for maxRPA and discuss how this property is connected to the existence of integrators [2].…”

Section: Preliminariesmentioning

confidence: 99%

Universal structural requirements for maximal robust perfect adaptation in biomolecular networks

Gupta

Khammash

2022

Preprint

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Consider a biomolecular reaction network that exhibits robust perfect adaptation to disturbances from several parallel sources. The well-known Internal Model Principle of control theory suggests that such systems must include a subsystem (called the "internal model") that is able to recreate the dynamic structure of the disturbances. This requirement poses certain structural constraints on the network which we elaborate in this paper for the scenario where constant-in-time disturbances maximally affect network interactions and there is model uncertainty and possible stochasticity in the dynamics. We prove that these structural constraints are primarily characterized by a simple linear-algebraic stoichiometric condition which remains the same for both deterministic and stochastic descriptions of the dynamics. Our results reveal the essential requirements for maximal robust perfect adaptation in biology, with important implications for both systems and synthetic biology. We exemplify our results through many known examples of robustly adapting networks and we construct new examples of such networks with the aid of our linear-algebraic characterization.

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Section: Preliminariesmentioning

confidence: 99%

Universal structural requirements for maximal robust perfect adaptation in biomolecular networks

Gupta

Khammash

2022

Preprint

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“…Biologically, perfect adaptation, in some cases known as homeostasis, is an important cellular function for maintaining the ability to respond to changing external stimulation while subsequently returning to an almost unperturbed level of internal components (Figure 1C ) ( 16 , 17 ); several adaptation circuit motifs have been identified. Synthetic robust perfect adaptation (RPA), as a high-performance adaptation function, is in high demand in synthetic biology ( 18 , 19 ).…”

Section: Introductionmentioning

confidence: 99%

Synthetic robust perfect adaptation achieved by negative feedback coupling with linear weak positive feedback

Sun

Wei

Zhang

et al. 2022

Nucleic Acids Research

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Unlike their natural counterparts, synthetic genetic circuits are usually fragile in the face of environmental perturbations and genetic mutations. Several theoretical robust genetic circuits have been designed, but their performance under real-world conditions has not yet been carefully evaluated. Here, we designed and synthesized a new robust perfect adaptation circuit composed of two-node negative feedback coupling with linear positive feedback on the buffer node. As a key feature, the linear positive feedback was fine-tuned to evaluate its necessity. We found that the desired function was robustly achieved when genetic parameters were varied by systematically perturbing all interacting parts within the topology, and the necessity of the completeness of the topological structures was evaluated by destroying key circuit features. Furthermore, different environmental perturbances were imposed onto the circuit by changing growth rates, carbon metabolic strategies and even chassis cells, and the designed perfect adaptation function was still achieved under all conditions. The successful design of a robust perfect adaptation circuit indicated that the top-down design strategy is capable of predictably guiding bottom-up engineering for robust genetic circuits. This robust adaptation circuit could be integrated as a motif into more complex circuits to robustly implement more sophisticated and critical biological functions.

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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

Salzano

Fiore

et al. 2022

Preprint

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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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Perfect adaptation in biology

Cited by 91 publications

References 56 publications

Universal structural requirements for maximal robust perfect adaptation in biomolecular networks

Universal structural requirements for maximal robust perfect adaptation in biomolecular networks

Synthetic robust perfect adaptation achieved by negative feedback coupling with linear weak positive feedback

Multicellular PI control for gene regulation in microbial consortia

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