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Analysis of primitive genetic interactions for the design of a genetic signal differentiator

Halter, Wolfgang and Murray, Richard M. and Allgöwer, Frank (2019) Analysis of primitive genetic interactions for the design of a genetic signal differentiator. Synthetic Biology, 4 (1). Art. No. ysz015. ISSN 2397-7000. https://resolver.caltech.edu/CaltechAUTHORS:20200131-125317403

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Abstract

We study the dynamic and static input–output behavior of several primitive genetic interactions and their effect on the performance of a genetic signal differentiator. In a simplified design, several requirements for the linearity and time-scales of processes like transcription, translation and competitive promoter binding were introduced. By experimentally probing simple genetic constructs in a cell-free experimental environment and fitting semi-mechanistic models to these data, we show that some of these requirements can be verified, while others are only met with reservations in certain operational regimes. Analyzing the linearized model of the resulting genetic network, we conclude that it approximates a differentiator with relative degree one. Taking also the discovered nonlinearities into account and using a describing function approach, we further determine the particular frequency and amplitude ranges where the genetic differentiator can be expected to behave as such.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1093/synbio/ysz015DOIArticle
ORCID:
AuthorORCID
Halter, Wolfgang0000-0001-9902-5782
Murray, Richard M.0000-0002-5785-7481
Additional Information:© 2019 The Author(s). Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Received: 28 February 2019; Revision received: 01 May 2019; Accepted: 28 May 2019; Published: 27 June 2019. The authors are grateful for Vipul Singhal, Andrey Shur, Anandh Swaminathan and William Poole from the Murray Lab at Caltech for the thought provoking discussions and support in the laboratory. This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft (DFG)) within the Cluster of Excellence in Simulation Technology (EXC 310/2) at the University of Stuttgart. Conflict of interest statement: None declared.
Funders:
Funding AgencyGrant Number
Deutsche Forschungsgemeinschaft (DFG)EXC 310/2
Subject Keywords:genetic circuit design; combinatorial promoters; signal differentiator
Issue or Number:1
Record Number:CaltechAUTHORS:20200131-125317403
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200131-125317403
Official Citation:Wolfgang Halter, Richard M Murray, Frank Allgöwer, Analysis of primitive genetic interactions for the design of a genetic signal differentiator, Synthetic Biology, Volume 4, Issue 1, 2019, ysz015, https://doi.org/10.1093/synbio/ysz015
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:101036
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:31 Jan 2020 20:59
Last Modified:12 Oct 2020 19:23

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