Modeling the effects of compositional context on promoter activity in an E. coli extract based transcription-translation system

One of the fundamental challenges in implementing complex biocircuits is understanding how the spatial arrangement of biological parts impacts biocircuit behavior. We develop a set of synthetic biology parts for systematically probing the effects of spatial arrangement on levels of transcription. Our initial experimental assays prove that even the rearrangement of two biocircuit parts (comprised of a promoter, coding sequence, and terminator) into three spatially distinct orientations (convergent, divergent, and tandem orientation) can exhibit significantly different levels of transcription. These findings motivate the need for mathematical models to describe these spatial context effects. We pose a novel nonlinear massaction kinetics based model that enables the integration of knowledge about spatial or compositional context and canonical descriptions of transcriptional dynamics. Our findings suggest that compositional context plays a role in biocircuit part performance and comprise an important piece of biocircuit interconnection theory.