Researchers Rewire Intracellular Signals for Use in Reengineering Biological Processes

Achievement date: 

University of California (UC) researchers from San Francisco and Berkeley worked collaboratively through the NSF-funded Synthetic Biology Engineering Research Center (SynBERC), headquartered at UC Berkeley, to successfully engineer new protein interactions able to control complex biological processes. This work opens up fresh opportunities to engineer biological circuits—a key need for achieving the potential of synthetic biology to improve human welfare through health, energy, and environmental applications.


Reengineering signaling proteins so that they function in cells is extremely difficult, as many requirements must be considered at the same time. This study used foundational computational protein design methods (developed within SynBERC) to rewire a cellular signaling pathway by directly modifying a protein-protein interface. The ability to computationally engineer highly-specific protein-protein interactions is a major step forward in developing engineering technologies for building useful biological systems from standard interchangeable parts.


SynBERC’s goal is to make biology easier to engineer. Computational design of protein interfaces promises to provide specific components that facilitate the predictable engineering of cellular functions. Considerable progress in engineering signaling circuits had been made by recombining commonly occurring domains. However, our ability to engineer cellular functions predictably was constrained by the complex signaling environment that is often present.

This research helped address the predictability problem by validating the design of the interface between a key signaling protein and its activator. The result opens new opportunities and augments existing approaches to engineer biological circuits.