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Negative autoregulation matches production and demand in synthetic transcriptional networks

Franco, Elisa; Giordano, Giulia LU ; Forsberg, Per Ola LU and Murray, Richard M. (2014) In ACS Synthetic Biology 3(8). p.589-599
Abstract

We propose a negative feedback architecture that regulates activity of artificial genes, or "genelets", to meet their output downstream demand, achieving robustness with respect to uncertain open-loop output production rates. In particular, we consider the case where the outputs of two genelets interact to form a single assembled product. We show with analysis and experiments that negative autoregulation matches the production and demand of the outputs: the magnitude of the regulatory signal is proportional to the "error" between the circuit output concentration and its actual demand. This two-device system is experimentally implemented using in vitro transcriptional networks, where reactions are systematically designed by optimizing... (More)

We propose a negative feedback architecture that regulates activity of artificial genes, or "genelets", to meet their output downstream demand, achieving robustness with respect to uncertain open-loop output production rates. In particular, we consider the case where the outputs of two genelets interact to form a single assembled product. We show with analysis and experiments that negative autoregulation matches the production and demand of the outputs: the magnitude of the regulatory signal is proportional to the "error" between the circuit output concentration and its actual demand. This two-device system is experimentally implemented using in vitro transcriptional networks, where reactions are systematically designed by optimizing nucleic acid sequences with publicly available software packages. We build a predictive ordinary differential equation (ODE) model that captures the dynamics of the system and can be used to numerically assess the scalability of this architecture to larger sets of interconnected genes. Finally, with numerical simulations we contrast our negative autoregulation scheme with a cross-activation architecture, which is less scalable and results in slower response times. © 2014 American Chemical Society.

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author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
in vitro, negative feedback, nucleic acid systems, synthetic biology, transcriptional circuits
in
ACS Synthetic Biology
volume
3
issue
8
pages
11 pages
publisher
American Chemical Society (ACS)
external identifiers
  • scopus:84906230280
DOI
10.1021/sb400157z
language
English
LU publication?
no
id
5ce8185b-e864-421d-ad17-237b0a9045eb
date added to LUP
2016-07-06 15:25:36
date last changed
2017-04-12 09:22:31
@article{5ce8185b-e864-421d-ad17-237b0a9045eb,
  abstract     = {<p>We propose a negative feedback architecture that regulates activity of artificial genes, or "genelets", to meet their output downstream demand, achieving robustness with respect to uncertain open-loop output production rates. In particular, we consider the case where the outputs of two genelets interact to form a single assembled product. We show with analysis and experiments that negative autoregulation matches the production and demand of the outputs: the magnitude of the regulatory signal is proportional to the "error" between the circuit output concentration and its actual demand. This two-device system is experimentally implemented using in vitro transcriptional networks, where reactions are systematically designed by optimizing nucleic acid sequences with publicly available software packages. We build a predictive ordinary differential equation (ODE) model that captures the dynamics of the system and can be used to numerically assess the scalability of this architecture to larger sets of interconnected genes. Finally, with numerical simulations we contrast our negative autoregulation scheme with a cross-activation architecture, which is less scalable and results in slower response times. © 2014 American Chemical Society.</p>},
  author       = {Franco, Elisa and Giordano, Giulia and Forsberg, Per Ola and Murray, Richard M.},
  keyword      = {in vitro,negative feedback,nucleic acid systems,synthetic biology,transcriptional circuits},
  language     = {eng},
  month        = {08},
  number       = {8},
  pages        = {589--599},
  publisher    = {American Chemical Society (ACS)},
  series       = {ACS Synthetic Biology},
  title        = {Negative autoregulation matches production and demand in synthetic transcriptional networks},
  url          = {http://dx.doi.org/10.1021/sb400157z},
  volume       = {3},
  year         = {2014},
}