Mathematical model of a serine integrase-controlled toggle switch with a single input

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
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stark, Professor William 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 > Institute of Molecular Cell and Systems Biology
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
589141A platform for rapid and precise DNA module rearrangements in Synthetic BiologyWilliam StarkBiotechnology and Biological Sciences Research Council (BBSRC)BB/K003356/1RI MOLECULAR CELL & SYSTEMS BIOLOGY