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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

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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:
DateEvent
June 2017Published
26 May 2017Accepted
28 February 2017Submitted
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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