Negative autoregulation matches production and demand in synthetic transcriptional networks
(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.
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- author
- Franco, Elisa ; Giordano, Giulia LU ; Forsberg, Per Ola LU and Murray, Richard M.
- organization
- publishing date
- 2014-08-15
- 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
- The American Chemical Society (ACS)
- external identifiers
-
- scopus:84906230280
- pmid:24697805
- ISSN
- 2161-5063
- 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
- 2024-04-05 01:56:08
@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.</p>}},
author = {{Franco, Elisa and Giordano, Giulia and Forsberg, Per Ola and Murray, Richard M.}},
issn = {{2161-5063}},
keywords = {{in vitro; negative feedback; nucleic acid systems; synthetic biology; transcriptional circuits}},
language = {{eng}},
month = {{08}},
number = {{8}},
pages = {{589--599}},
publisher = {{The 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}},
doi = {{10.1021/sb400157z}},
volume = {{3}},
year = {{2014}},
}