Nature Biotechnol. http://doi.org/kpk (2013)

By taking advantage of specific interactions between genes and proteins, living cells with synthetic genetic circuits that either retain memory of an activating event or perform cellular logic — for example, detecting a certain molecule in the environment and generating a specific response — can be created. Now, Piro Siuti et al. report a strategy to assemble cellular circuits that combine both logic and memory. They built all possible two-input logic functions in living Escherichia coli cells by assembling a variety of DNA-based modules (promoters, terminators and outputs of gene expression) that control the production of green fluorescent protein (output) as a function of the expression of two serine recombinases — enzymes that can cut, flip or insert strands of DNA depending on the orientation of two DNA recognition sites. The expression of the recombinases is activated by two signalling molecules (inputs), and alters the gene modules permanently. Hence, the recombinase-based logic gates can maintain memory of input events (over tens of generations in cell division), and also over time, therefore also making sequential logic possible.