Title: Automated design of biological circuits
Authors: Guillermo Rodrigo, Javier Carrera and Alfonso Jaramillo
Abstract:Synthetic Biology has relied until now on rational design techniques to create novel functional genetic networks allowing the reprogramming of cells. However, their increasing size and complexity requires starting demanding computational methods able to integrate current knowledge and to complement the design principles of biological circuits. This requires unsupervised methods, which among them are those that mimic evolution to engineer biological networks. Circuits are computationally evolved by modifying the promoters, genes and/or nucleotide sequences, and by using appropriate fitness functions. This provides the way to evolve their regulation or their kinetic parameters towards a targeted behaviour. These automatic approaches have been applied to design transcription, nucleic acids and metabolic networks. For genetic networks, we use phenomenological models that could be assembled in a combinatorial way to generate a given circuit. In this way, we have constructed an artificial registry of models, which includes combinatorial promoters, from existing characterisation data. Those models provide the means of incorporating experimental data back into the design process. We illustrate our procedures by the design of band detectors, counters and logic gates. In the case of RNA circuits, we show how to design asRNA-based circuits working as logic devices in E. coli.
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