PROGRAMME DE STAGE D’INITIATION A LA RECHERCHE AU 1ER CYCLE
SIRI
Université de Lyon/Université d’Ottawa
Appel à candidature 2017
Title
Supervisor-­‐s
Institute
rRNA
epigenetics: role of
heterogeneity in tumorigenesis?
ribosome MARCEL Virginie
[email protected]
+3 (0)4 26 5 6 45
Cancer Research Center of Lyon (CRCL)
located on the Centre Léon Bérard Hospital site
http://www.crcl.fr
Lab
Team “Nuclear domains and pathologies”
Dir. Jean-­‐Jacques DIAZ
http://www.crcl.fr/Domaines-­‐nucleaires-­‐et-­‐pathologies.crcl.fr
Context Ribosome are ribonucleoprotein complexes that translate the
mRNAs into proteins. For a long time, ribosome has been thought
to be a unique entity. However, it appears that ribosome can
display different compositions depending on the physio-­‐
pathological contexts to drive specific translational reprogram-­‐
ming and thus directly contribute in the establishment of
particular cellular phenotypes. One main source of ribosome
heterogeneity comes from chemical modifications of ribosomal
RNA (rRNA) that include 2’O-­‐ribose methylation. We recently
reported that alteration of 2’O-­‐ribose methylation profile
affects translation of a subset of mRNAs encoding oncogenic
proteins (IGF-­‐1R, CMYC, VEGFA, FGF1) (Marcel et al, Cancer Cell
2013).
The team project aims at determining the role of ribosome
heterogeneity in tumorigenesis with the goal to use in the near
future the ribosome as a novel clinical biomarker and an original
target in anti-­‐cancer therapies.
Abstract/Objectives
At present, we developed two distinct projects dedicated to
(1) determine the contribution of ribosome heterogeneity in defining breast cancer subtypes, and in particular in defining the
triple negative breast cancer subtype through the Epithelial-­‐to-­‐
Mesenchymal Transition biological process;
(2) determine the contribution of ribosome in promoting
resistance to targeted therapies in non-­‐small cell lung cancers.
The trainee will participate in investigating the impact of
ribosome composition alterations in translational control
and tumorigenesis.
Several technics will be used:
-­‐ Cell culture (cell maintenance, transfection…)
-­‐ Cellular biology (real time proliferation,
invasion/migration assays, enzymatic assays…)
-­‐ Molecular biology (qPCR, Western blot…)
real
time
This training could be combined with the CO-­‐OP programs.
Bibliography
1. Marcel, V., Catez, F., Diaz, J.-­‐J., 2015. Ribosome heterogeneity in
tumorigenesis: the rRNA point of view. Molecular & Cellular
Oncology 2, e983755.
2. Marcel, V., Catez, F., Diaz, J.-­‐J., 2013. Ribosomes: the future of targeted therapies? Oncotarget 4, 1554–1555.
3. Marcel, V., Ghayad, S.E., Belin, S., Thérizols, G., Morel, A.-­‐P.,
Solano-­‐Gonzàlez, E., Vendrell, J.A., Hacot, S., Mertani, H.C., Albaret,
M.A., Bourdon, J.-­‐C., Jordan, L., Thompson, A., Tafer, Y., Cong, R., Bouvet, P., Saurin, J.-­‐C., Catez, F., Prats, A.-­‐C., Puisieux, A., Diaz, J.-­‐J.,
2013. p53 Acts as a Safeguard of Translational Control by
Regulating Fibrillarin and rRNA Methylation in Cancer. Cancer
Cell 24, 318–330.
Location Duration Language
(French/English/Both)
CRCL – CLB
Cheney A 4th floor
28 rue Laennec
69008 LYON
FRANCE
Summer 2017 (from May to July)
French
English