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IGH Thesis topic : Seitz team, IGH  CNRS

 

Gene regulation by microRNAs : from molecules to the organism

Gene regulation and homeostasis are two universal principles in the living world. Each one has been well studied, and current analysis methods allowed major advances in their understanding. But they have never been analyzed from the same perspective, even though they exhibit an intrinsic antagonism : gene regulation tends to alter the response of biological systems, while homeostatic mechanisms tend to give them inertia. Unexpected characteristics appear to emerge from their confrontation.

This PhD project deals with the antagonism between homeostasis and one mode of gene regulation : repression by microRNAs. These regulatory RNAs repress their targets to a very small extent (less than 2-fold), while interacting with many targets (a few hundreds of targets per mammalian microRNA). Current target identification methods (based on molecular biology and bio-informatics) tend to neglect that quantitative aspect.

The PhD project aims at identifying microRNA/mRNA interactions that trigger phenotypic consequences at the organism scale, among the numerous microRNA/mRNA interactions happening at the molecular scale. Drosophila genetics, cell culture and bio-informatics analyses now offer efficient tools for the precise interrogation of macroscopic consequences of molecular interactions (through CRISPR/Cas9 genome editing, high-throughput molecular biology, measurement of phylogenetic conservation on hundreds of genomes, ...).

Our lab is specialized in microRNA biology, using equally experimental biology and bio-informatics. Training young researchers is very important to us (every former lab member has published his/her work with us, and all of them still work in research), as well as the involvement of young researchers in the definition of strategies and research projects. We are located in the institute of human genetics (UMR 9002, CNRS and Montpellier univ.). More information on our work and our publications : on our lab’s website.

Candidates are encouraged to compete for a PhD fellowship from the CBS2 graduate school in order to apply