Model-based redesign of global transcription regulation.

J. Carrera (1, 2) , G. Rodrigo (2) , A. Jaramillo (3, 4)

1 Instituto de Aplicaciones en Tecnologias de la Informacion y las Comunicaciones Avanzadas
2 IBMCP - Instituto de Biologia Molecular y Celular de Plantas
3 BIOC - Laboratoire de Biochimie de l'Ecole polytechnique
4 Programme d'Épigénomique

Synthetic biology aims to the design or redesign of biological systems. In particular, one possible goal could be the rewiring of the transcription regulation network by exchanging the endogenous promoters. To achieve this objective, we have adapted current methods to the inference of a model based on ordinary differential equations that is able to predict the network response after a major change in its topology. Our procedure utilizes microarray data for training. We have experimentally validated our inferred global regulatory model in Escherichia coli by predicting transcriptomic profiles under new perturbations. We have also tested our methodology in silico by providing accurate predictions of the underlying networks from expression data generated with artificial genomes. In addition, we have shown the predictive power of our methodology by obtaining the gene profile in experimental redesigns of the E. coli genome, where rewiring the transcriptional network by means of knockouts of master regulators or by upregulating transcription factors controlled by different promoters. Our approach is compatible with most network inference methods, allowing to explore computationally future genome-wide redesign experiments in synthetic biology.

Domaines: Biochimie, Biologie Moléculaire

J. Carrera, G. Rodrigo, A. Jaramillo. Model-based redesign of global transcription regulation.. Nucleic Acids Research, 2009, 37 (5), pp.e38. ⟨10.1093/nar/gkp022⟩. ⟨hal-00766032⟩