Construction of Synthetic Circuits by Harnessing Orthogonal Genetic Parts

Many applications require cells to integrate multiple environmental signals and to implement synthetic control over biological processes.  Genetic circuits enable cells to perform computational operations, interfacing biosensor modules and actuator modules.  Despite advances in the rational construction of artificial biological systems, synthetic biologists are still limited by the lack of well-characterized orthogonal parts and predictive computational models.  Here, we harness a toolbox of genetic parts from bacteria to construct a genetic multiplexer, three 2-input AND gates, a 3-input AND gate, and a 4-input AND gate.  To this end, genetic parts have been screened and modified to make them orthogonal, a transfer function model has been developed, and such well-characterized modules have been rationally combined.  This work represents a step toward constructing programmed cells that are able to process multiple input signals and to produce desirable outputs for real-world applications.