LAPSE:2019.0612
Published Article
LAPSE:2019.0612
Mechanistic Models of Inducible Synthetic Circuits for Joint Description of DNA Copy Number, Regulatory Protein Level, and Cell Load
Lorenzo Pasotti, Massimo Bellato, Davide De Marchi, Paolo Magni
July 5, 2019
Accurate predictive mathematical models are urgently needed in synthetic biology to support the bottom-up design of complex biological systems, minimizing trial-and-error approaches. The majority of models used so far adopt empirical Hill functions to describe activation and repression in exogenously-controlled inducible promoter systems. However, such equations may be poorly predictive in practical situations that are typical in bottom-up design, including changes in promoter copy number, regulatory protein level, and cell load. In this work, we derived novel mechanistic steady-state models of the lux inducible system, used as case study, relying on different assumptions on regulatory protein (LuxR) and cognate promoter (Plux) concentrations, inducer-protein complex formation, and resource usage limitation. We demonstrated that a change in the considered model assumptions can significantly affect circuit output, and preliminary experimental data are in accordance with the simulated activation curves. We finally showed that the models are identifiable a priori (in the analytically tractable cases) and a posteriori, and we determined the specific experiments needed to parametrize them. Although a larger-scale experimental validation is required, in the future the reported models may support synthetic circuits output prediction in practical situations with unprecedented details.
Keywords
bottom-up design, cell load, copy number, inducible promoter, mathematical modeling, mechanistic model, synthetic biology
Subject
Suggested Citation
Pasotti L, Bellato M, De Marchi D, Magni P. Mechanistic Models of Inducible Synthetic Circuits for Joint Description of DNA Copy Number, Regulatory Protein Level, and Cell Load. (2019). LAPSE:2019.0612
Author Affiliations
Pasotti L: Laboratory of Bioinformatics, Mathematical Modelling and Synthetic Biology, Department of Electrical, Computer and Biomedical Engineering, University of Pavia, I-27100 Pavia, Italy; Centre for Health Technologies, University of Pavia, I-27100 Pavia, Italy [ORCID]
Bellato M: Laboratory of Bioinformatics, Mathematical Modelling and Synthetic Biology, Department of Electrical, Computer and Biomedical Engineering, University of Pavia, I-27100 Pavia, Italy; Centre for Health Technologies, University of Pavia, I-27100 Pavia, Italy
De Marchi D: Laboratory of Bioinformatics, Mathematical Modelling and Synthetic Biology, Department of Electrical, Computer and Biomedical Engineering, University of Pavia, I-27100 Pavia, Italy; Centre for Health Technologies, University of Pavia, I-27100 Pavia, Italy
Magni P: Laboratory of Bioinformatics, Mathematical Modelling and Synthetic Biology, Department of Electrical, Computer and Biomedical Engineering, University of Pavia, I-27100 Pavia, Italy; Centre for Health Technologies, University of Pavia, I-27100 Pavia, Italy [ORCID]
[Login] to see author email addresses.
Journal Name
Processes
Volume
7
Issue
3
Article Number
E119
Year
2019
Publication Date
2019-02-26
Published Version
ISSN
2227-9717
Version Comments
Original Submission
Other Meta
PII: pr7030119, Publication Type: Journal Article
Record Map
Published Article

LAPSE:2019.0612
This Record
External Link

doi:10.3390/pr7030119
Publisher Version
Download
Files
[Download 1v1.pdf] (2.9 MB)
Jul 5, 2019
Main Article
License
CC BY 4.0
Meta
Record Statistics
Record Views
552
Version History
[v1] (Original Submission)
Jul 5, 2019
 
Verified by curator on
Jul 5, 2019
This Version Number
v1
Citations
Most Recent
This Version
URL Here
https://psecommunity.org/LAPSE:2019.0612
 
Original Submitter
Calvin Tsay
Links to Related Works
Directly Related to This Work
Publisher Version