Profil N° (à remplir par VAS) FINANCEMENT

Profil N° (à remplir par VAS)
FINANCEMENT Demandé
Acquis
Fiche Résumé du sujet de thèse 2017
Champs disciplinaire Autres et Autres
Titre de la thèse : (1-2 lignes)
Identification and characterization of Iqub, a new Cancer/Testis (CT) gene.
3 mots-clés : (1 ligne)
CT antigen / spermatogenesis / immunotherapy
ACRONYME
CANTES
Unité/équipe encadrante :
Inserm U1085 IRSET, group REMEDE
Nom du responsable scientifique
Soazik Jamin
nom du codirecteur le cas échéant :
Michael Primig
Contact :
[email protected]
Contexte socioéconomique et scientifique : (10 lignes)
The death rate of cancer remains high in spite of the development of numerous therapies. Approaches
based on immunotherapy are beginning to replace or complement chemotherapy. The identification of
novel target proteins is therefore an essential step for these new promising treatments. We propose to
study IQUB, a new Cancer/Testis gene (CT gene). These genes are a key element of methods that
involve a patient’s immune system. IQUB is de-repressed in in all somatic cancers that we analyzed
using GeneChip expression data from a very large cancer study published by a US consortium.
Moreover, mutations in IQUB have been associated with gastric cancer. This makes the gene an
interesting candidate for the development of novel immunotherapies. Analysis of a transgenic mouse
model should reveal the molecular mechanism and the signaling pathway involved in its potential role
as an oncogene. Little is known about IQUB but protein interaction data point to several functions and
possible association with a member of the CT gene founding protein MAGE.
Les hypothèses et questions posées (8 lignes)
We hypothesize that understanding IQUB’s essential role in meiosis and gametogenesis will help
uncover its proposed mechanism of action during somatic cancer progression. It is therefore essential
to first understand IQUB’s role in germ cell interaction and differentiation before determining its
possible function in somatic cancer development. IQUB was deleted in a mouse model by KOMP
(Knockout Mouse Project) and the transgenic animals are available for further analysis. The
homozygote males are infertile (published in the database of the International Mouse Phenotyping
Consortium IMPC, www.impc.org). However, the phenotype is not understood at the histological and
molecular level and the functions of IQUB remain unknown.
Les grandes étapes de la thèse et démarche (10-12 lignes)
The project will be done along three axes. First, the target gene expression profile will be determined at
the level of RNA and protein on testicular sections and TMAs (Tissue MicroArrays) of different cancers in
comparison to their corresponding healthy tissues. Then the mouse phenotype will be analyzed to ask
how spermatogenesis in altered and which step is affected. Different marker proteins will be studied.
IQUB is probably involved in cell-cell interactions via cilia in the germline. Interaction data suggest
IQUB to be a hub protein that binds different regulatory proteins and known CT genes. Finally, we will
use different in vitro cell lines to study the protein’s role in cell division and differentiation to help
assess its value as a target for immunotherapy.
Approches méthodologiques et techniques envisagées (4-6 lignes)
The student will employ molecular biological (PCR, in situ hybridization, cloning), biochemical
(immunohistochemistry and immunofluorescence) and cell biological (transfection) methods.
Compétences scientifiques et techniques requises par le candidat (2 lignes)
This project requires training in molecular biology and/or biochemistry.