Modeling the Effects of Compositional Context on Promoter Activity in an E. Coli Extract based Transcription-Translation System

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Enoch Yeung, Andrew Ng, Jongmin Kim, Zachary Z. Sun, and Richard M. Murray
2014 Conference on Decision and Control (CDC)

One of the fundamental challenges in synthesizing complex biocircuits from existing biocircuit components is understanding how the spatial arrangement of biocircuit components impacts component behavior. In this paper we develop a set of synthetic biology parts for systematically probing the effects of spatial arrangement on transcriptional expression. 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 transcriptions. These findings motivate the need for mathematical models to describe these spatial context effects. We pose a novel nonlinear mass-action 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 is a key factor in determining bio- circuit part performance and thus represent another important piece in biocircuit interconnection theory.