Mechanistic modelling of a recombinase-based two-input temporal logic gate
Autor: | Wilson W. Wong, Jack E. Bowyer, Declan G. Bates, Victoria Hsiao |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
two-input temporal logic gate circuit enzymes dna ENCODE biological boolean logic operations Boolean algebra site-specific recombinases mechanistic modelling 03 medical and health sciences symbols.namesake dna sequence in vitro genetic switches serine integrases Recombinase molecular biophysics Temporal logic genetics recombinase-based two-input temporal logic gate QH426 lcsh:QH301-705.5 boolean algebra Communication 030102 biochemistry & molecular biology biology business.industry fungi ssr protein dna sequence in vivo Integrases Expression (mathematics) Integrase 030104 developmental biology lcsh:Biology (General) Logic gate logic gates biology.protein symbols serine-integrase-mediated dna inversion Biological system business boolean logic gates |
Zdroj: | Engineering Biology (2017) |
ISSN: | 2398-6182 |
DOI: | 10.1049/enb.2017.0006 |
Popis: | 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. |
Databáze: | OpenAIRE |
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