Development and experimental validation of a mechanistic model of a recombinase-based temporal logic gate

Abstract

DNA recombination provides an ideal mechanism for constructing stable and reversible synthetic biological switches. Recent advances in recombinase-based circuitry that account for more than one protein input have been shown to enable the construction of circuits with temporal Boolean logic operations in vivo. Associated mathematical models have to date only captured the qualitative dynamical features of such systems and are thus of limited utility as tools to aid in the design of such circuitry. Here we develop a detailed mechanistic model of a two-input temporal logic gate circuit based on unidirectional DNA recombination with bacteriophage integrases to detect and encode sequences of input events. The model is validated against in vivo experimental data and is shown to quantitatively replicate and predict key dynamical features of the logic gate.