Synthetic Genetic Reversible Feynman Gate in a Single E. coli Cell and Its Application in Bacterial to Mammalian Cell Information Transfer.

ABSTRACT

Reversible computing is a nonconventional form of computing where the inputs and outputs are mapped in a unique one-to-one fashion. Reversible logic gates in single living cells have not been demonstrated. Here, we constructed a synthetic genetic reversible Feynman gate in single E. coli cells, and the input-output relations were measured in a clonal population. The inputs were extracellular chemicals, isopropyl ß-d-1-thiogalactopyranoside (IPTG), and anhydrotetracycline (aTc), and the outputs were two fluorescence proteins. We developed a simple mathematical model and simulation to capture the essential features of the circuit and experimentally demonstrated that the behavior of the circuit was ultrasensitive and predictive. We showed an application by creating an intercellular Feynman gate, where input information from bacteria was computed and transferred to HeLa cells through shRNAs delivery and the output signals were observed as silencing of native AKT1 and CTNNB1 genes. The introduction of reversible logics in synthetic biology is new, and given that one-to-one input-output mapping, such reversible genetic systems might have applications in sensing, diagnostics, cellular computing, and synthetic biology.