An N-stage cascade of phosphorylation cycles as an insulation device for synthetic biological circuits

Shah, Rushina; Vecchio, Domitilla Del

doi:10.1109/ecc.2016.7810557

Cited by 3 publications

(2 citation statements)

References 18 publications

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“…The ratio

can thus be tuned such that the system satisfies test (iii) with

. However, if the different stages of the cycle share a common phosphatase, additional cycles may be required to maintain a linear input-output response ( 50 ). Details of this analysis are shown in step 5 of Supporting Material , Section 1.7.…”

Section: Resultsmentioning

confidence: 99%

Signaling Architectures that Transmit Unidirectional Information Despite Retroactivity

Shah

Vecchio

2017

Biophysical Journal

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A signaling pathway transmits information from an upstream system to downstream systems, ideally in a unidirectional fashion. A key obstacle to unidirectional transmission is retroactivity, the additional reaction flux that affects a system once its species interact with those of downstream systems. This raises the fundamental question of whether signaling pathways have developed specialized architectures that overcome retroactivity and transmit unidirectional signals. Here, we propose a general procedure based on mathematical analysis that provides an answer to this question. Using this procedure, we analyze the ability of a variety of signaling architectures to transmit one-way (from upstream to downstream) signals, as key biological parameters are tuned. We find that single stage phosphorylation and phosphotransfer systems that transmit signals from a kinase show a stringent design tradeoff that hampers their ability to overcome retroactivity. Interestingly, cascades of these architectures, which are highly represented in nature, can overcome this tradeoff and thus enable unidirectional transmission. By contrast, phosphotransfer systems, and single and double phosphorylation cycles that transmit signals from a substrate, are unable to mitigate retroactivity effects, even when cascaded, and hence are not well suited for unidirectional information transmission. These results are largely independent of the specific reaction-rate constant values, and depend on the topology of the architectures. Our results therefore identify signaling architectures that, allowing unidirectional transmission of signals, embody modular processes that conserve their input/output behavior across multiple contexts. These findings can be used to decompose natural signal transduction networks into modules, and at the same time, they establish a library of devices that can be used in synthetic biology to facilitate modular circuit design.

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“…The ratio

can thus be tuned such that the system satisfies test (iii) with

Section: Resultsmentioning

confidence: 99%

Signaling Architectures that Transmit Unidirectional Information Despite Retroactivity

Shah

Vecchio

2017

Biophysical Journal

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“…(5) In signaling systems, covalent cycles that have fast turnover have been shown to help insulate modules because they are able to supply adequate signaling protein for downstream processes while being minimally susceptible to retroactivity due to the separation of timescales. [16,156,157] Fold-change and ratiometric detection…”

Section: Solutionmentioning

confidence: 99%

Design patterns of biological cells

Andrews,

Wiley,

Sauro

2024

BioEssays

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Design patterns are generalized solutions to frequently recurring problems. They were initially developed by architects and computer scientists to create a higher level of abstraction for their designs. Here, we extend these concepts to cell biology to lend a new perspective on the evolved designs of cells' underlying reaction networks. We present a catalog of 21 design patterns divided into three categories: creational patterns describe processes that build the cell, structural patterns describe the layouts of reaction networks, and behavioral patterns describe reaction network function. Applying this pattern language to the E. coli central metabolic reaction network, the yeast pheromone response signaling network, and other examples lends new insights into these systems.

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