Computational re-design of synthetic genetic oscillators for independent amplitude and frequency modulation
File(s)
Published version
Author(s)
Tomazou, Marios
Barahona, Mauricio
Polizzi, Karen
Stan, G
Type
Journal Article
Abstract
To perform well in biotechnology applications, synthetic genetic oscillators must be engineered to allow independent modulation of amplitude and period. This need is currently unmet. Here, we demonstrate computationally how two classic genetic oscillators, the dual-feedback oscillator and the repressilator, can be re-designed to provide independent control of amplitude and period and improve tunability—that is, a broad dynamic range of periods and amplitudes accessible through the input “dials.” Our approach decouples frequency and amplitude modulation by incorporating an orthogonal “sink module” where the key molecular species are channeled for enzymatic degradation. This sink module maintains fast oscillation cycles while alleviating the translational coupling between the oscillator's transcription factors and output. We characterize the behavior of our re-designed oscillators over a broad range of physiologically reasonable parameters, explain why this facilitates broader function and control, and provide general design principles for building synthetic genetic oscillators that are more precisely controllable.
Date Issued
2018-04-25
Date Acceptance
2018-03-19
Citation
Cell Systems, 2018, 6 (4), pp.508-520.e5
ISSN
2405-4712
Publisher
Elsevier
Start Page
508
End Page
520.e5
Journal / Book Title
Cell Systems
Volume
6
Issue
4
Copyright Statement
© 2018 The Author(s). Published by Elsevier Inc.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Identifier
https://www.cell.com/cell-systems/fulltext/S2405-4712(18)30110-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2405471218301108%3Fshowall%3Dtrue
Grant Number
EP/M002187/1
EP/P009352/1
EP/N014529/1
EP/I032223/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
ESCHERICHIA-COLI
EXPRESSION
REPRESSOR
DYNAMICS
DEGRADATION
ACTIVATION
ROBUST
LIGHT
biosensors
computational biology
genetic oscillators
mutual information
orthogonal amplitude and period modulation
periodic signal generator in biology
protease
robustness
synthetic biology
Biofeedback, Psychology
Biosensing Techniques
Biotechnology
Gene Expression Regulation
Gene Regulatory Networks
Models, Biological
Models, Genetic
Signal Transduction
Synthetic Biology
Transcription Factors
Transcription, Genetic
Transcription Factors
Biosensing Techniques
Biotechnology
Signal Transduction
Transcription, Genetic
Gene Expression Regulation
Models, Biological
Models, Genetic
Gene Regulatory Networks
Biofeedback, Psychology
Synthetic Biology
0601 Biochemistry and Cell Biology
Publication Status
Published
Date Publish Online
2018-04-18