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Post-doctoral position : genome-wide analysis of SMARCB1-deficient SWI/SNF complex function in rhabdoid tumours

ABG-47839 Emploi Junior
14/11/2017 CDD 24 Mois > 25 et < 35 K€ brut annuel
I2BC
Gif-sur-Yvette/Saclay - Ile-de-France - France
  • Biochimie
  • Biologie
Epigenome, chromatin remodellers, genome-wide analysis, rhaboid tumours
Recherche et Développement

Employeur

The Institute for Integrative Biology of the Cell (I2BC) UMR 9198 is a “Unité Mixte de Recherche” (joint research unit ; UMR ) supported by both Université Paris-Sud, the CNRS and the CEA.
The Institute regroup 80 teams of scientists, 15 technological facilities from 8 research units (CGM, IBBMC, IGM, ISV, LEBS, VMS, SB2SM, SBiGeM)
The Institute is in 3 research campus (Orsay Campus of the Université Paris Sud, Gif Sur Yvette Campus of CNRS, and Saclay Campus of CEA) with 14 buildings. All the I2BC activities will be join on the Gif-sur-Yvette Campus in 2018.

Poste et missions

A post-doctoral position is open in the team of Matthieu GERARD at the institute for integrative biology of the cell (I2BC, Gif-sur-Yvette, France) to study how alterations in the function of ATP-dependent chromatin remodellers trigger the formation of rhabdoid tumours.
ATP-dependent chromatin remodelling factors (‘remodellers’) are essential for correct chromosome structure and function. Remodellers perform diverse roles that include facilitating nucleosome assembly and disassembly, transiently exposing nucleosomal DNA and nucleosome sliding. Recently, the GERARD team has systematically investigated the function of a large number of remodellers in embryonic stem (ES) cells, thereby revealing their links with gene expression and enhancer function (de Dieuleveult et al. Nature 2016; PMID: 26814966).
Large scale tumour exome sequencing revealed that the genes encoding the 15 subunits of the human SWI/SNF remodeller are mutated in more than 20% of human cancers. The SWI/SNF SMARCB1 subunit has been found mutated in virtually 100% of rhabdoid tumours, which are aggressive infantile tumours frequently located in the central nervous system.
Based on the expertise of the GERARD team on chromatin remodelling and in genome-wide approaches, the post-doc will investigate the contribution to oncogenesis of two distinct molecular mechanisms :
First, the he/she will use a genome-wide strategy to define the function of the residual, SMARCB1-deficient SWI/SNF complex, which is thought to have oncogenic properties.
Second, we identified two other remodellers that play a function antagonist to that of SWI/SNF in the regulation of transcription. These remodellers may thus be important actors in the oncogenic process when the function of SWI/SNF in altered by SMARCB1 loss-of-function. The post-doc will test this hypothesis, using both ES cells and a mouse model of rhabdoid tumours. These studies, which will be realized in collaboration with the team of Franck Bourdeaut (Institut Curie, Paris), should allow us to propose new therapeutic strategies to treat these infantile tumours.

Mobilité géographique :

Pas de déplacement

Prise de fonction :

01/02/2018

Profil

We are looking for an enthusiastic, recently graduated PhD student. The hired post-doc will be in charge of doing both the wet biology experiments and the associated bioinformatics analysis. Applicants should have a strong background in molecular biology and biochemistry. A prior experiment in genome-wide approaches and bioinformatics would be an advantage but is not mandatory, as this expertise will be acquired in the host laboratory.
 

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