Systematic and synthetic approaches to rewire regulatory networks.

Microbial gene regulatory networks are composed of cis- and trans-components that in concert act to control essential and adaptive cellular functions. Regulatory components and interactions evolve to adopt new configurations through mutations and network rewiring events, resulting in novel phenotypes that may benefit the cell. Advances in high-throughput DNA synthesis and sequencing have enabled the development of new tools and approaches to better characterize and perturb various elements of regulatory networks. Here, we highlight key recent approaches to systematically dissect the sequence space of cis-regulatory elements and trans-regulators as well as their inter-connections. These efforts yield fundamental insights into the architecture, robustness, and dynamics of gene regulation and provide models and design principles for building synthetic regulatory networks for a variety of practical applications.