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Olivier Martin

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SémIDEEV à l’UMR Génétique Quantitative et Évolution – Le Moulon


Ferme du Moulon – Salle de conférences

Vendredi  29  mars  2019


Matthew  DEYELL

Invité par Christine Dillmann

Multiplexed Genetic Perturbations of the Regulatory Network of E. coli


Understanding how gene expression is regulated is a necessary piece of how phenotypes emerge from a given genotype. The complex structure of this transcriptional regulatory network is believed to be significant to the transcriptional response of a cell.
However it is unclear how highly entangled interactions between regulatory hubs control global gene expression patterns. Here we use a programmable DNA binding protein called CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) to perturb gene expression of global regulators within the transcriptional regulatory network. The CRISPR system allows us to perturb these regulators in all possible combinations, including higher order perturbations with potentially all targeted global regulators perturbed at the same time. We record both the expression pattern of the transcriptome using RNA sequencing, and the fitness of each strain with growth curves.
We find significant high order epistasis between global transcription regulators. The pair-wise epistasis between global transcription factors relies on the presence or absence of other perturbations. This implies that other perturbations could act as potentiating mutations.
Finally we map the fitness and phenotype for each perturbation. This reveals that global transcriptional regulators work together to adjust the trajectory of gene expression across different environments. These different trajectories allow the cell to optimize the cell’s fitness to variable growth conditions.