Pokhilko, A., Ebenhöh, O., Stark, W. M. and Colloms, S. D. (2018) Mathematical model of a serine integrase-controlled toggle switch with a single input. Journal of the Royal Society: Interface, 15(143), 20180160. (doi: 10.1098/rsif.2018.0160) (PMID:29875284) (PMCID:PMC6030632)
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Abstract
Dual-state genetic switches that can change their state in response to input signals can be used in synthetic biology to encode memory and control gene expression. A transcriptional toggle switch (TTS), with two mutually repressing transcription regulators, was previously used for switching between two expression states. In other studies, serine integrases have been used to control DNA inversion switches that can alternate between two different states. Both of these switches use two different inputs to switch ON or OFF. Here, we use mathematical modelling to design a robust one-input binary switch, which combines a TTS with a DNA inversion switch. This combined circuit switches between the two states every time it receives a pulse of a single-input signal. The robustness of the switch is based on the bistability of its TTS, while integrase recombination allows single-input control. Unidirectional integrase-RDF-mediated recombination is provided by a recently developed integrase-RDF fusion protein. We show that the switch is stable against parameter variations and molecular noise, making it a promising candidate for further use as a basic element of binary counting devices.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Stark, Professor Marshall and Colloms, Dr Sean and Pokhilko, Dr Alexandra |
Authors: | Pokhilko, A., Ebenhöh, O., Stark, W. M., and Colloms, S. D. |
College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
Journal Name: | Journal of the Royal Society: Interface |
Publisher: | Royal Society |
ISSN: | 1742-5689 |
ISSN (Online): | 1742-5662 |
Published Online: | 06 June 2018 |
Copyright Holders: | Copyright © 2018 The Authors |
First Published: | First published in Journal of the Royal Society Interface 15(143):20180160 |
Publisher Policy: | Reproduced under a Creative Commons License |
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