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Synthetic negative feedback circuits using engineered small RNAs
- Source :
- Nucleic Acids Research
- Publication Year :
- 2017
- Publisher :
- Cold Spring Harbor Laboratory, 2017.
-
Abstract
- Negative feedback is known to endow biological and man-made systems with robust performance in the face of uncertainties and disturbances. To date, synthetic biological feedback circuits have relied upon protein-based, transcriptional regulation to control circuit output. Small RNAs (sRNAs) are non-coding RNA molecules which can inhibit translation of target messenger RNAs (mRNAs). In this paper, we designed, modelled and built two synthetic negative feedback circuits that use rationally-designed sRNAs for the first time. The first circuit builds upon the well characterisedtet-based autorepressor, incorporating an externally-inducible sRNA to tune the effective feedback strength. This allows more precise fine-tuning of the circuit output in contrast to the sigmoidal input-output response of the autorepressor alone. In the second circuit, the output is a transcription factor that induces expression of an sRNA which negatively regulates the translation of the mRNA encoding this output, creating direct, closed-loop, negative feedback. Analysis of the noise profiles of both circuits showed that the use of sRNAs did not result in large increases in noise. Stochastic and deterministic modelling of both circuits agreed well with experimental data. Finally, simulations using fitted parameters allowed dynamic attributes of each circuit such as response time and disturbance rejection to be investigated.
- Subjects :
- Fine-tuning
05 Environmental Sciences
F100
Synthetic biological circuit
Topology (electrical circuits)
H800
Biology
Bioinformatics
03 medical and health sciences
Synthetic biology
Encoding (memory)
Negative feedback
Escherichia coli
RNA, Messenger
030304 developmental biology
Electronic circuit
Feedback, Physiological
08 Information And Computing Sciences
0303 health sciences
Models, Genetic
C100
030302 biochemistry & molecular biology
RNA
06 Biological Sciences
C700
Repressor Proteins
RNA, Bacterial
Gene Expression Regulation
RNA, Small Untranslated
Synthetic Biology and Bioengineering
Biological system
Developmental Biology
Plasmids
Subjects
Details
- ISSN :
- 03051048
- Database :
- OpenAIRE
- Journal :
- Nucleic Acids Research
- Accession number :
- edsair.doi.dedup.....ce3e7b8d05e1ea8a9dac0833b1296932