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.
Highlights
Genetic switches with two states (ON/OFF) are essential components of synthetic biology memory and counting devices, with potential application in biotechnology, biosensors and biocomputing [1,2,3]
During the construction of the inversion-and-transcriptional toggle switch (ITTS), we initially considered a simpler scheme with int and integrase-RDF fusion protein (intRDF) expressed from a constitutive promoter in an invertible DNA segment
The simultaneous expression of int and intRDF is avoided in our final design due to the tight control of int and intRDF expression by the transcriptional toggle switch (TTS), as described below
Summary
Genetic switches with two states (ON/OFF) are essential components of synthetic biology memory and counting devices, with potential application in biotechnology, biosensors and biocomputing [1,2,3]. The creation of these binary switches is, an important goal of synthetic biology. An orthogonal set of single-input state-based toggle switches with this behaviour could be used to encode the digits in a binary ripple counter [2] In such a counter, each switch represents a single binary digit, and N interconnected switches would be able to count up to 2N21 occurrences of the same repeated signal. No singleinput switch capable of robust toggling between two states has been implemented to date
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