LAPSE:2019.0539
Published Article
LAPSE:2019.0539
Component Characterization in a Growth-Dependent Physiological Context: Optimal Experimental Design
Nathan Braniff, Matthew Scott, Brian Ingalls
April 15, 2019
Synthetic biology design challenges have driven the use of mathematical models to characterize genetic components and to explore complex design spaces. Traditional approaches to characterization have largely ignored the effect of strain and growth conditions on the dynamics of synthetic genetic circuits, and have thus confounded intrinsic features of the circuit components with cell-level context effects. We present a model that distinguishes an activated gene’s intrinsic kinetics from its physiological context. We then demonstrate an optimal experimental design approach to identify dynamic induction experiments for efficient estimation of the component’s intrinsic parameters. Maximally informative experiments are chosen by formulating the design as an optimal control problem; direct multiple-shooting is used to identify the optimum. Our numerical results suggest that the intrinsic parameters of a genetic component can be more accurately estimated using optimal experimental designs, and that the choice of growth rates, sampling schedule, and input profile each play an important role. The proposed approach to coupled component⁻host modelling can support gene circuit design across a range of physiological conditions.
Keywords
cell physiology, characterization, host-context effects, model fitting, optimal control, optimal experimental design, synthetic biology
Suggested Citation
Braniff N, Scott M, Ingalls B. Component Characterization in a Growth-Dependent Physiological Context: Optimal Experimental Design. (2019). LAPSE:2019.0539
Author Affiliations
Braniff N: Department of Applied Mathematics, University of Waterloo, Waterloo, ON N2L 3G1, Canada
Scott M: Department of Applied Mathematics, University of Waterloo, Waterloo, ON N2L 3G1, Canada
Ingalls B: Department of Applied Mathematics, University of Waterloo, Waterloo, ON N2L 3G1, Canada [ORCID]
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Journal Name
Processes
Volume
7
Issue
1
Article Number
E52
Year
2019
Publication Date
2019-01-21
Published Version
ISSN
2227-9717
Version Comments
Original Submission
Other Meta
PII: pr7010052, Publication Type: Journal Article
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LAPSE:2019.0539
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doi:10.3390/pr7010052
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Apr 15, 2019
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CC BY 4.0
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[v1] (Original Submission)
Apr 15, 2019
 
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Apr 15, 2019
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v1
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https://psecommunity.org/LAPSE:2019.0539
 
Original Submitter
Calvin Tsay
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