Generation of Intracellular Logic Gates with Two Orthogonal Chemically Inducible Systems

In the creation of non-silicon-based computers, various biomolecules have been used to construct Boolean logic gates. However, their ‘computational’ timescale is relatively slow (tens of minutes to hours), as most of these biological logic gates utilize gene expression that requires time-consuming processes such as transcription and translation. For faster processing, we employed chemically inducible protein dimerization systems. To rapidly trigger two chemically inducible signals, we developed an efficient chemical dimerization system using a newly synthesized analog of the plant hormone gibberellin (GA3-AM) and its binding proteins, a system that is completely orthogonal to rapamycin-mediated protein dimerization (Movie #1). With the two chemical inputs (rapamycin and GA3-AM), we achieved AND as well as OR gates, that produced output signals such as fluorescence and membrane ruffling on a timescale of seconds. The use of two orthogonal dimerization systems in the same cell also allows for finer modulation of protein perturbations than is possible with a single dimerizer. We are now working to create more complex logic gates as well as multiplexed logic gates for further complex computations.
Schematic of AND gate employing rapamycin and gibberellin chemical dimerization systems. (Miyamoto et al. Nat Chem Biol, 2012)