Theoretical Design of Paradoxical Signaling-Based Synthetic Population Control Circuit in E. coli

Title	Theoretical Design of Paradoxical Signaling-Based Synthetic Population Control Circuit in E. coli
Authors	Michaëlle N. Mayalu, Richard M. Murray
Source	2020 Winter q-bio
Abstract	We have developed a mathematical framework to analyze the cooperative control of cell population homeostasis via paradoxical signaling in synthetic contexts. Paradoxical signaling functions through quorum sensing (where cells produce and release a chemical signal as a function of cell density). Precisely, the same quorum sensing signal provides both positive (proliferation) and negative (death) feedback in different signal concentration regimes. As a consequence, the relationship between intercellular quorum sensing signal concentration and net growth rate (cell proliferation minus death rates) can be non-monotonic. This relationship is a condition for robustness to certain cell mutational overgrowths and allows for increased stability in the presence of environmental perturbations. Here, we explore stability and robustness of a conceptualized synthetic circuit. Furthermore, we asses possible design principles that could exist among a subset of paradoxical circuit implementations. This analysis sparks the development a bio-molecular control theory to identify ideal underlying characteristics for paradoxical signaling control systems.
Type	Conference paper
URL	https://www.biorxiv.org/content/10.1101/2020.01.27.921734v1
Tag	mm20-wqbio
ID	2019i
Funding	DARPA BioCon
Flags	Biocircuits