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PhD Defense: Amélie DARD

When Oct 13, 2016
from 02:00 PM to 05:00 PM
Where Salle de thèse, ENS de Lyon
Contact Name

On Thursday 13th of October at 14:00 pm Amélie DARD from Samir MERABET's team (Ontogenesis and molecular interactions) will defend her thesis (in french) entitled:

 

"Décryptage des interactions moléculaires entre les protéines HOX et leurs partenaires"

(Deciphering the molecular interactions between Hox proteins and their partners.)

 

The venue is iSalle des Thèses Chantal Rabourdin-Combe (ENS, Monod campus)

 

Abstract:

Hox genes are present in the vast majority of the animal kingdom, and are required for the differentiation of several longitudinal axes during embryogenesis. There are also involved in the homeostasis of several tissues in the adult organism. Mutations affecting their expression and/or function are found in numerous human cancers.

Hox genes encode for transcription factors that recognize short and highly similar DNA-binding sites. The direct interaction between Hox proteins and two evolutionary classes of cofactors, the Pbx and Meis proteins, allows them to recognize more specific DNA-binding sites. This interaction was first described to rely on a common short Hox protein motif called hexapeptide (HX). However, subsequent functional and molecular analyses showed that the HX motif could be dispensable for the interaction with Pbx and Meis partner in vivo. These results strongly suggest that Hox proteins could use different motifs to interact with the same set of cofactors. Such alternative motifs are unknown in mammalian Hox proteins.

My thesis work is dedicated to the issue of the role of the HX motif and other short motifs in Hox-cofactor interactions. More particularly, I developed two main projects using human Hox proteins and cell lines derived from different tissues as a model system. My first project consisted in the systematic analysis of the interaction property of all Hox paralogs with the Pbx/Meis cofactors. This work revealed new Pbx/Meis-interaction interfaces in human Hox proteins. My second project consisted in establishing a new molecular screen to identify transcriptional partners of the wild type or HX-mutated human HoxA9 protein in different cell lines.

Overall, my thesis work opens new perspectives into our understanding of the molecular mode of action of Hox proteins and their cofactors, in a normal or pathological developmental context.