Model of Paradoxical Signaling Regulated T-Cell Population Control for Design of Synthetic Circuits

Title	Model of Paradoxical Signaling Regulated T-Cell Population Control for Design of Synthetic Circuits
Authors	Michaelle N. Mayalu and Harman Mehta and Richard M. Murray
Source	Submitted, 2019 European Control Conference (ECC)
Abstract	Paradoxical signaling occurs when the same sig- naling molecule can trigger antagonistic cell functions. For example, T-Cells secret cytokine IL-2 which promotes T-Cell proliferation and also affects cell death. It has been shown that cells with this signaling capability have bi-stable population dynamics and can achieve identical levels of population homeostasis independent of initial cell concentrations. These capabilities are desirable in the context of synthetic population control circuits designed for application in therapeutic treatment of various diseases. It thus becomes important to understand the dependence of the cell system on the intracellular paradoxical components and to develop accurate models to provide insight into optimal design characteristics. Here, we create a model that integrates three IL-2 driven intracellular mechanisms that trigger 1) T-cell proliferation 2) T-cell apoptosis and 3) IL-2 production. Using this model, we are able to explore the internal mechanisms necessary for paradoxical signaling in T-Cells. It was shown that the intracellular mechanisms considered were sufficient to produce population dynamic characteristics of paradoxical signaling consistent with published systems level models and data. Furthermore, analysis of parameters revealed dependency of population homeostatic stability on the production and activation of the specific intracellular proteins considered.
Type	Conference paper
URL	http://www.cds.caltech.edu/~murray/preprints/mhm19-ecc s.pdf
DOI
Tag	mhm19-ecc
ID	2018f
Funding	DARPA BioCon
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