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System identification of phosophorylation based insulator in a cell-free in vitro transcription-translation system
Abstract An outstanding challenge in the design of …
An outstanding challenge in the design of synthetic biocircuits is the development of a robust and efficient strategy for interconnecting functional modules. Recent theoretical work demonstrated that a phosphorylation based insulator implementing a dual strategy of high gain and strong negative feedback could potentially serve as a device to attenuate retroactivity. This research investigates the structural identifiability of the phoshorylation based insulator when implemented in an {\it in vitro} transcription-translation cell free expression system. We consider a complex model that provides an intricate description of all chemical reactions and leveraging specific physiologically plausible assumptions, we derive a rigorous simplified model that captures the output dynamics of the phosphorylation based insulator. We perform standard system identification analysis and determine that the model is globally identifiable with respect to three critical parameters. Our findings show the utility of the transcription-translation cell free expression system as a platform for system identification, as it provides extra control inputs for parameter estimation that typically are unavailable in vivo. The parameters estimated are then used as a basis for a simulation study in a parallel experimental work (also submitted to qBio-2014).
mental work (also submitted to qBio-2014).  +
Authors Enoch Yeung, Shaobin Guo, Richard M. Murray  +
Funding Model-guided Discovery and Optimization of Cell-based Sensors + , Biomolecular Breadboards for Prototyping and Debugging Synthetic Biocircuits +
ID 2013l  +
Source Submitted, 2014 Winter q-bio Conference (5 Nov 2013)  +
Tag ygm14-wqbio  +
Title System identification of phosophorylation based insulator in a cell-free in vitro transcription-translation system +
Type Conference Paper  +
Categories Papers
Modification date
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15 May 2016 06:15:04  +
URL
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http://www.cds.caltech.edu/~murray/preprints/ygm14-wqbio_s.pdf  +
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System identification of phosophorylation based insulator in a cell-free in vitro transcription-translation system + Title
 

 

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