Project Description

Following an initial period of growth after the publication of the first synthetic gene circuits, development in the field has stalled. This is due in part to the limited number of well-characterized parts with desired features. For instance, the function of the repressilator and genetic toggle switch both rely on repressible promoters with high cooperativity – provided in these cases by multimerization of the repressor proteins. The TALE family of transcription factors (TFs) and the CRISPR/Cas9 system show promise in expanding the parts list to bind to near-arbitrary target sequences, but because they bind to DNA as monomers, promoters under their control cannot show cooperativity in their response.

It has been shown theoretically and in vivo that repressors binding as monomers to multiple binding sites can introduce cooperativity in to a system. With this in mind, we are developing an organism-independent approach that leverages programmable TFs to create library of independent and orthogonal repressor-promoter pairs with a range of expression parameters (viz. cooperativity, basal and maximal expression rate, response time) of potentially unlimited size. It is our aim that this approach will enable the field to move toward exploring higher-order dynamics.