Next Article in Journal
Realizing Energy Savings in Integrated Process Planning and Scheduling
Next Article in Special Issue
Computational Methods Enabling Next-Generation Bioprocesses
Previous Article in Journal
An Integrated Delphi-AHP and Fuzzy TOPSIS Approach toward Ranking and Selection of Renewable Energy Resources in Pakistan
Previous Article in Special Issue
Distilling Robust Design Principles of Biocircuits Using Mixed Integer Dynamic Optimization
 
Search for Articles:
Title / Keyword
Author / Affiliation
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
Journals
Processes
Volume 7
Issue 3
10.3390/pr7030119
processes-logo
Submit to this Journal Review for this Journal Edit a Special Issue
► Article Menu

Article Menu

share announcement question_answer thumb_up
...
textsms
...
Article

Mechanistic Models of Inducible Synthetic Circuits for Joint Description of DNA Copy Number, Regulatory Protein Level, and Cell Load

by
Lorenzo Pasotti
1,2,*,
Massimo Bellato
1,2,
Davide De Marchi
1,2 and
Paolo Magni
1,2
1
Laboratory of Bioinformatics, Mathematical Modelling and Synthetic Biology, Department of Electrical, Computer and Biomedical Engineering, University of Pavia, I-27100 Pavia, Italy
2
Centre for Health Technologies, University of Pavia, I-27100 Pavia, Italy
*
Author to whom correspondence should be addressed.
Processes 2019, 7(3), 119; https://doi.org/10.3390/pr7030119
Received: 14 December 2018 / Revised: 5 February 2019 / Accepted: 19 February 2019 / Published: 26 February 2019
(This article belongs to the Special Issue Computational Synthetic Biology)
View Full-Text Download PDF
Browse Figures

Abstract

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. View Full-Text
Keywords: mathematical modeling; mechanistic model; synthetic biology; copy number; inducible promoter; cell load; bottom-up design mathematical modeling; mechanistic model; synthetic biology; copy number; inducible promoter; cell load; bottom-up design
►▼ Show Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
SciFeed

Share and Cite

MDPI and ACS Style

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. Processes 2019, 7, 119. https://doi.org/10.3390/pr7030119

AMA Style

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. Processes. 2019; 7(3):119. https://doi.org/10.3390/pr7030119

Chicago/Turabian Style

Pasotti, Lorenzo, Massimo Bellato, Davide De Marchi, and Paolo Magni. 2019. "Mechanistic Models of Inducible Synthetic Circuits for Joint Description of DNA Copy Number, Regulatory Protein Level, and Cell Load" Processes 7, no. 3: 119. https://doi.org/10.3390/pr7030119

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Article Access Map by Country/Region

1
Back to TopTop