A fungicide-responsive kinase as a tool for synthetic cell fate regulation.
Nucleic Acids Res
; 43(14): 7162-70, 2015 Aug 18.
Article
en En
| MEDLINE
| ID: mdl-26138483
Engineered biological systems that precisely execute defined tasks have major potential for medicine and biotechnology. For instance, gene- or cell-based therapies targeting pathogenic cells may replace time- and resource-intensive drug development. Engineering signal transduction systems is a promising, yet presently underexplored approach. Here, we exploit a fungicide-responsive heterologous histidine kinase for pathway engineering and synthetic cell fate regulation in the budding yeast Saccharomyces cerevisiae. Rewiring the osmoregulatory Hog1 MAPK signalling system generates yeast cells programmed to execute three different tasks. First, a synthetic negative feedback loop implemented by employing the fungicide-responsive kinase and a fungicide-resistant derivative reshapes the Hog1 activation profile, demonstrating how signalling dynamics can be engineered. Second, combinatorial integration of different genetic parts including the histidine kinases, a pathway activator and chemically regulated promoters enables control of yeast growth and/or gene expression in a two-input Boolean logic manner. Finally, we implemented a genetic 'suicide attack' system, in which engineered cells eliminate target cells and themselves in a specific and controllable manner. Taken together, fungicide-responsive kinases can be applied in different constellations to engineer signalling behaviour. Sensitizing engineered cells to existing chemicals may be generally useful for future medical and biotechnological applications.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regulación de la Expresión Génica
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Proteínas Quinasas Activadas por Mitógenos
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Sistema de Señalización de MAP Quinasas
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Proteínas de Saccharomyces cerevisiae
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Ingeniería Celular
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Antifúngicos
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2015
Tipo del documento:
Article
País de afiliación:
Suecia
Pais de publicación:
Reino Unido