The idea of combining man-made and natural systems has fascinated humans for centuries. However, despite the explosion of life science advances, the integration of electronic and biological systems remains woefully underdeveloped. To address this, we will apply principles of Synthetic Biology to develop biological cells controlled by electronic signals.

We propose to create synthetic cellular receptors selectively activated by electrochemically activated peptide. In order to endow the system with the ability to activate a selected ligand:receptor pair in the presence of other polypeptides, we propose to construct peptide-selective bio-electrodes. Electro activation of the peptides decreases their affinity for the electrode and leads to its relocation to the two component cellular receptor that utilizes intramolecular proteolysis to activate transcription of the reporter genes. Using the team’s expertise in protein, cellular and electronic engineering we will design an integrated system where the activation of the reporter expression can be both controlled and monitored using electrode array in a few or even in a single mammalian cell.

This proposed approach enables the construction of a potentially unlimited number of orthogonal electrode/ peptide/receptor systems that allow multichannel information transfer between computing devices and biological cells. While the first embodiment relies on the relatively slow gene expression readout, the same approach can be used to control practically any biochemical process in real time. Such synthetic signaling pathways capable of performing logical operations will exert complex and precise control on cellular biology, leading to a first generation of bioelectronic hybrids.