DNA-RNA-Iinspired computing, Molecular programming of logic gates in bacteria
The computational design of RNA interactions allows for the programming of complex information processing devices in bacteria. For this, we use evolutionary computation algorithms that automatically optimize the RNA sequences by minimizing the energy of formation and the activation energy. An automated design approach has been already reported in vitro, but never before in living cells. We have experimentally validated in E. coli fully synthetic RNAs displaying logic gate behavior. We also show in E. coli that our riboregulatory devices can be combined with known functional RNA fragments (ribozymes and aptamers) to create complex logic circuits in bacteria. We also characterized their in vivo RNA dynamics by using microfluidics time-lapse microscopy to track single-cells. Our work provides a new paradigm to program functional RNAs gates working in living cells by allowing the computer to use first principles combined with a molecular interaction mechanism.