Computational Methods for the Design of Recombinase Logic Circuits with Adaptable Circuit Specifications.

Synthetic biology aims at engineering new biological systems and functions that can be used to provide new technological solutions to worldwide challenges. Detection and processing of multiple signals are crucial for many synthetic biology applications. A variety of logic circuits operating in living cells have been implemented. One particular class of logic circuits uses site-specific recombinases mediating specific DNA inversion or excision. Recombinase logic offers many interesting features, including single-layer architectures, memory, low metabolic footprint, and portability in many species. Here, we present two automated design strategies for both Boolean and history-dependent recombinase-based logic circuits. One approach is based on the distribution of computation within multicellular consortia, and the other is a single-cell design. Both are complementary and adapted for non-expert users via a web design interface, called CALIN and RECOMBINATOR, for multicellular and single-cell design strategies, respectively. In this book chapter, we are guiding the reader step by step through recombinase logic circuit design, from selecting the design strategy fitting to their final system of interest to obtaining the final design using one of our design web interfaces.