Design and construction of a versatile synthetic network for bistable gene expression in mammalian systems

A Polynikis, G. Cuccato, S. Criscuolo, SJ Hogan, M Di Bernardo, D. di Bernardo

Research output: Contribution to journalArticle (Academic Journal)peer-review

3 Citations (Scopus)

Abstract

We constructed and modeled a novel synthetic network which may be able to exhibit bistable expression of a reporter gene in mammalian cells. This network is based on an aptamer-fused short-hairpin RNA (shRNA) directed against a single mRNA encoding both a EGFP reporter gene and the repressor tTR-KRAB, which, in turn, represses transcription of the shRNA. The activity of the shRNA can be controlled by an inducer molecule (theophylline) which prevents the aptamer-fused shRNA to be properly processed. Repression of the tTR-KRAB can be relieved by treatment with doxycyline. This reciprocal negative feedback loop can exhibit a bistable response, as shown through the mathematical analysis performed here. Specifically, the network can be controlled to induce sustained expression of a shRNA, or the reporter gene, with a transient input of two different inducer molecules.
Translated title of the contributionDesign and construction of a versatile synthetic network for bistable gene expression in mammalian systems
Original languageEnglish
Pages (from-to)195 - 203
Number of pages8
JournalJournal of Computational Biology
Volume18 Issue 2
DOIs
Publication statusPublished - Feb 2011

Structured keywords

  • Bristol BioDesign Institute
  • Engineering Mathematics Research Group

Keywords

  • synthetic biology

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