Robust set-point regulation of gene expression using resource competition couplings in mammalian cells
File(s)ACC_2022.pdf (484.44 KB)
Accepted version
Author(s)
Perrino, Giansimone
Stan, Guy-Bart
Type
Conference Paper
Abstract
Gene expression depends on the cellular con-text. One major contributor to gene expression variability is competition for limited transcriptional and translational re-sources, which may induce indirect couplings among otherwise independently-regulated genes. Here, we apply control theoretical concepts and tools to design an incoherent feedforward loop (iFFL) biomolecular controller operating in mammalian cells using translational-resource competition couplings. Harnessing a resource-aware mathematical model, we demonstrate analytically and computationally that our resource-aware design can achieve near-constant set-point regulation of gene expression whilst ensuring robustness to plasmid uptake variation. We also provide an analytical condition on the model parameters to guide the design of the resource-aware iFFL controller ensuring robustness and performance in set-point regulation. Our theoretical design based on translational-resource competition couplings represents a promising approach to build more sophisticated resource-aware control circuits operating at the host-cell level.
Date Issued
2022-09-05
Date Acceptance
2022-09-01
Citation
2022 AMERICAN CONTROL CONFERENCE (ACC), 2022, pp.1373-1378
Publisher
IEEE
Start Page
1373
End Page
1378
Journal / Book Title
2022 AMERICAN CONTROL CONFERENCE (ACC)
Copyright Statement
Copyright © 2022 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000865458701059&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
Source
American Control Conference (ACC)
Subjects
Science & Technology
Technology
Automation & Control Systems
Publication Status
Published
Start Date
2022-06-08
Finish Date
2022-06-10
Coverage Spatial
Atlanta, GA
Date Publish Online
2022-09-05