2.50
Hdl Handle:
http://hdl.handle.net/10033/124205
Title:
Bimodal and hysteretic expression in mammalian cells from a synthetic gene circuit.
Authors:
May, Tobias; Eccleston, Lee; Herrmann, Sabrina; Hauser, Hansjörg; Goncalves, Jorge; Wirth, Dagmar
Abstract:
In order to establish cells and organisms with predictable properties, synthetic biology makes use of controllable, synthetic genetic devices. These devices are used to replace or to interfere with natural pathways. Alternatively, they may be interlinked with endogenous pathways to create artificial networks of higher complexity. While these approaches have been already successful in prokaryotes and lower eukaryotes, the implementation of such synthetic cassettes in mammalian systems and even animals is still a major obstacle. This is mainly due to the lack of methods that reliably and efficiently transduce synthetic modules without compromising their regulation properties. To pave the way for implementation of synthetic regulation modules in mammalian systems we utilized lentiviral transduction of synthetic modules. A synthetic positive feedback loop, based on the Tetracycline regulation system was implemented in a lentiviral vector system and stably integrated in mammalian cells. This gene regulation circuit yields a bimodal expression response. Based on experimental data a mathematical model based on stochasticity was developed which matched and described the experimental findings. Modelling predicted a hysteretic expression response which was verified experimentally. Thereby supporting the idea that the system is driven by stochasticity. The results presented here highlight that the combination of three independent tools/methodologies facilitate the reliable installation of synthetic gene circuits with predictable expression characteristics in mammalian cells and organisms.
Affiliation:
Department of Gene Regulation and Differentiation, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Citation:
Bimodal and hysteretic expression in mammalian cells from a synthetic gene circuit. 2008, 3 (6):e2372 PLoS ONE
Journal:
PloS one
Issue Date:
2008
URI:
http://hdl.handle.net/10033/124205
DOI:
10.1371/journal.pone.0002372
PubMed ID:
18523635
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
Publications of Dept. Gene Regulation and Differentiation (RDIF)

Full metadata record

DC FieldValue Language
dc.contributor.authorMay, Tobiasen
dc.contributor.authorEccleston, Leeen
dc.contributor.authorHerrmann, Sabrinaen
dc.contributor.authorHauser, Hansjörgen
dc.contributor.authorGoncalves, Jorgeen
dc.contributor.authorWirth, Dagmaren
dc.date.accessioned2011-03-11T09:19:18Z-
dc.date.available2011-03-11T09:19:18Z-
dc.date.issued2008-
dc.identifier.citationBimodal and hysteretic expression in mammalian cells from a synthetic gene circuit. 2008, 3 (6):e2372 PLoS ONEen
dc.identifier.issn1932-6203-
dc.identifier.pmid18523635-
dc.identifier.doi10.1371/journal.pone.0002372-
dc.identifier.urihttp://hdl.handle.net/10033/124205-
dc.description.abstractIn order to establish cells and organisms with predictable properties, synthetic biology makes use of controllable, synthetic genetic devices. These devices are used to replace or to interfere with natural pathways. Alternatively, they may be interlinked with endogenous pathways to create artificial networks of higher complexity. While these approaches have been already successful in prokaryotes and lower eukaryotes, the implementation of such synthetic cassettes in mammalian systems and even animals is still a major obstacle. This is mainly due to the lack of methods that reliably and efficiently transduce synthetic modules without compromising their regulation properties. To pave the way for implementation of synthetic regulation modules in mammalian systems we utilized lentiviral transduction of synthetic modules. A synthetic positive feedback loop, based on the Tetracycline regulation system was implemented in a lentiviral vector system and stably integrated in mammalian cells. This gene regulation circuit yields a bimodal expression response. Based on experimental data a mathematical model based on stochasticity was developed which matched and described the experimental findings. Modelling predicted a hysteretic expression response which was verified experimentally. Thereby supporting the idea that the system is driven by stochasticity. The results presented here highlight that the combination of three independent tools/methodologies facilitate the reliable installation of synthetic gene circuits with predictable expression characteristics in mammalian cells and organisms.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshGenes, Syntheticen
dc.subject.meshHumansen
dc.subject.meshLentivirusen
dc.subject.meshMiceen
dc.subject.meshNIH 3T3 Cellsen
dc.subject.meshTransduction, Geneticen
dc.titleBimodal and hysteretic expression in mammalian cells from a synthetic gene circuit.en
dc.typeArticleen
dc.contributor.departmentDepartment of Gene Regulation and Differentiation, Helmholtz Centre for Infection Research, Braunschweig, Germany.en
dc.identifier.journalPloS oneen

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