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

Mayalu, Michaëlle N. and Mehta, Harman and Murray, Richard M. (2019) Model of Paradoxical Signaling Regulated T-Cell Population Control for Design of Synthetic Circuits. In: 2019 18th European Control Conference (ECC). IEEE , Piscataway, NJ, pp. 2152-2158. ISBN 978-3-907144-00-8. https://resolver.caltech.edu/CaltechAUTHORS:20190822-160825121

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Abstract

Paradoxical signaling occurs when the same signaling 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. Cells can achieve identical levels of population homeostasis for initial cell concentrations within the region of attraction. 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 bistability on the production and activation of the specific intracellular proteins considered.


Item Type:Book Section
Related URLs:
URLURL TypeDescription
https://doi.org/10.23919/ECC.2019.8795764DOIArticle
ORCID:
AuthorORCID
Mayalu, Michaëlle N.0000-0002-9678-0157
Murray, Richard M.0000-0002-5785-7481
Additional Information:© 2019 EUCA. This research is partially supported by the Defense Advanced Research Projects Agency (Agreement HR0011-17-2-0008). The content of the information does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred. The authors would like to thank Cindy Ren, Yitong Ma, Mark Budde and Michael Elowitz for their insightful discussion.
Funders:
Funding AgencyGrant Number
Defense Advanced Research Projects Agency (DARPA)HR0011-17-2-0008
Record Number:CaltechAUTHORS:20190822-160825121
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190822-160825121
Official Citation:M. N. Mayalu, H. Mehta and R. M. Murray, "Model of Paradoxical Signaling Regulated T-Cell Population Control for Design of Synthetic Circuits," 2019 18th European Control Conference (ECC), Naples, Italy, 2019, pp. 2152-2158. doi: 10.23919/ECC.2019.8795764
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:98137
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:22 Aug 2019 23:16
Last Modified:03 Oct 2019 21:38

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