A major goal of chemical and synthetic biologists is to create ligand–dependent genetic control systems to report on cellular metabolism, construct synthetic gene circuits, or reprogram cellular behavior. Synthetic riboswitches are ideal for these purposes because they can regulate the expression of any gene in response to any ligand that is capable of binding RNA, without the need for protein engineering. We have shown that synthetic riboswitches can direct the migration of E. coli cells toward novel ligands that are not recognized by wild–type cells. Using a riboswitch that represses gene expression, it is also possible to reprogram cells to migrate only in the absence of ligand.

Because the differences in cell motility at various ligand concentrations were easy to distinguish visually, we asked whether cell motility differences could be the basis of a high–throughput selection to discover synthetic riboswitches. The resulting motility–based selection method enables both positive and negative selections to discover rare events from large genetic libraries, yet is rapid, efficient, and inexpensive. We anticipate that ligand–dependent cell motility will be useful, both as a tool for high–throughput selections and as a phenotype for future applications in synthetic biology.

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