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Published June 27, 2019 | Submitted + Published + Supplemental Material
Journal Article Open

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

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.

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.

Attached Files

Published - ysz015.pdf

Submitted - ham19-oupsynbio_s.pdf

Supplemental Material - ysz015_supplementary_data.pdf

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August 22, 2023
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