Control engineering meets synthetic biology: Foundations and applications

Synthetic Biology enables the construction of new genetic circuits with the final goal of controlling cellular behaviour. However, the noisy nature of biomolecular interactions renders a fine regulation of such circuits necessary for their correct operation. A possible solution is cybergenetics, a new discipline merging the tools of Synthetic biology with those of control theory. Biomolecular controllers can be classified into three different categories (i) embedded, in which the controller is implemented as a genetic circuit co-existing in the same cell with the process to be controlled; (ii) external, where the controller is implemented as a software in a computer; (iii) multicellular, in which the controller and the process to be controlled are in two different cell populations. Here, we describe the advantages and drawbacks of each one of the approaches, expounding their main advantages, limitations, and applications.