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Mechanistic modelling of a recombinase-based two-input temporal logic gate
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Bowyer, Jack E., Hsiao, Victoria, Wong, Wilson W. and Bates, Declan (2017) Mechanistic modelling of a recombinase-based two-input temporal logic gate. Engineering Biology, 1 (1). pp. 40-50. doi:10.1049/enb.2017.0006
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Official URL: http://dx.doi.org/10.1049/enb.2017.0006
Abstract
Site-specific recombinases (SSRs) mediate efficient manipulation of DNA sequences in vitro and in vivo. In particular, serine integrases have been identified as highly effective tools for facilitating DNA inversion, enabling the design of genetic switches that are capable of turning the expression of a gene of interest on or off in the presence of a SSR protein. The functional scope of such circuitry can be extended to biological Boolean logic operations by incorporating two or more distinct integrase inputs. To date, mathematical modelling investigations have captured the dynamical properties of integrase logic gate systems in a purely qualitative manner, and thus such models are of limited utility as tools in the design of novel circuitry. Here, the authors develop a detailed mechanistic model of a two-input temporal logic gate circuit that can detect and encode sequences of input events. Their model demonstrates quantitative agreement with time-course data on the dynamics of the temporal logic gate, and is shown to subsequently predict dynamical responses relating to a series of induction separation intervals. The model can also be used to infer functional variations between distinct integrase inputs, and to examine the effect of reversing the roles of each integrase on logic gate output.
| Item Type: | Journal Article | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Subjects: | Q Science > QH Natural history > QH426 Genetics | ||||||||
| Divisions: | Faculty of Science > Engineering | ||||||||
| Library of Congress Subject Headings (LCSH): | Genetic recombination, Gene expression, Synthetic biology | ||||||||
| Journal or Publication Title: | Engineering Biology | ||||||||
| Publisher: | IET Digital Library | ||||||||
| ISSN: | 2398-6182 | ||||||||
| Official Date: | June 2017 | ||||||||
| Dates: |
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| Volume: | 1 | ||||||||
| Number: | 1 | ||||||||
| Page Range: | pp. 40-50 | ||||||||
| DOI: | 10.1049/enb.2017.0006 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access | ||||||||
| Funder: | Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), National Science Foundation (U.S.) (NSF) | ||||||||
| Grant number: | BB/P011926/1 (BBSRC), NSF#1614642 (NSF) |
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