Cellular Signaling Circuits Interfaced with Synthetic, Post-Translational, Negating Boolean Logic Devices

A negating
functionality is fundamental to information processing
of logic circuits within cells and computers. Aiming to adapt unutilized
electronic concepts to the interrogation of signaling circuits in
cells, we first took a bottom-up strategy whereby we created protein-based
devices that perform negating Boolean logic operations such as NOT,
NOR, NAND, and N-IMPLY. These devices function in living cells within
a minute by precisely commanding the localization of an activator
molecule among three subcellular spaces. We networked these synthetic
gates to an endogenous signaling circuit and devised a physiological
output. In search of logic functions in signal transduction, we next
took a top–down approach and computationally screened 108 signaling
pathways to identify commonalities and differences between these biological
pathways and electronic circuits. This combination of synthetic and
systems approaches will guide us in developing foundations for deconstruction
of intricate cell signaling, as well as construction of biomolecular
computers.