Rational design of modular circuits for gene transcription: a test of the bottom-up approach
Author(s)
Ceroni, F
Furini, S
Giordano, E
Cavalcanti, S
Type
Journal Article
Abstract
BACKGROUND: Most of synthetic circuits developed so far have been designed by an ad hoc approach, using a small number of components (i.e. LacI, TetR) and a trial and error strategy. We are at the point where an increasing number of modular, inter-changeable and well-characterized components is needed to expand the construction of synthetic devices and to allow a rational approach to the design. RESULTS: We used interchangeable modular biological parts to create a set of novel synthetic devices for controlling gene transcription, and we developed a mathematical model of the modular circuits. Model parameters were identified by experimental measurements from a subset of modular combinations. The model revealed an unexpected feature of the lactose repressor system, i.e. a residual binding affinity for the operator site by induced lactose repressor molecules. Once this residual affinity was taken into account, the model properly reproduced the experimental data from the training set. The parameters identified in the training set allowed the prediction of the behavior of networks not included in the identification procedure. CONCLUSIONS: This study provides new quantitative evidences that the use of independent and well-characterized biological parts and mathematical modeling, what is called a bottom-up approach to the construction of gene networks, can allow the design of new and different devices re-using the same modular parts.
Date Issued
2010-11-11
Date Acceptance
2010-11-11
Citation
Journal of Biological Engineering, 2010, 4 (14)
ISSN
1754-1611
Publisher
BioMed Central
Journal / Book Title
Journal of Biological Engineering
Volume
4
Issue
14
Copyright Statement
© Ceroni et al 2010. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
PII: 1754-1611-4-14
Subjects
Biotechnology
Publication Status
Published