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Stage proposé par
Nom et adresse de l’Unité : Inserm U1085 IRSET ; 9 rue du Prof. Léon Bernard, 35000 Rennes
Téléphone : 06 50 11 45 45
Mail : [email protected]
Site internet : www.irset.org
Directeur du Laboratoire ou de l’Unité : Bernard Jégou
Intitulé de l ‘équipe d’accueil : REMEDE
Prénom et NOM des Responsables de l’équipe : Michael Primig, Charles Pineau
Résumé du thème de recherche de l’équipe
Our long-term goals are to (i) participate in the global effort to complete the human proteome with
emphasis on testicular proteins, (ii) unravel genetic causes for male infertility and develop better
diagnostic tools to identify patients suitable for assisted reproductive technology, (iii) identify and
characterize novel testicular genes that encode suitable target proteins for the development of anticancer immunotherapy approaches (Cancer/Testis genes), (iv) study mechanisms controlling cell
division and differentiation that involve DNA binding regulatory proteins, the exoribonucleases
Rrp6/EXOSC10 and long non-coding RNAs, and (v) understand the mechanisms of cytotoxicity and
resistance against the widely used anti-cancer drug 5-FU, which inhibits Rrp6/EXOSC10.
Titre du projet de stage :
Expression and cellular localisation of novel Cancer/Testis antigens
for cancer immunotherapy
Prénom, NOM, téléphone et adresse e-mail du Responsable du stage: Michael Primig, 06 50 11
45 45 ; [email protected]
Projet de stage :
Immunotherapy is arguably among the most vibrant fields in oncology. Cancer/Testis antigens have
been used as targets to develop immunotherapeutical anti-cancer treatments since many years. We
have carried out a large-scale GeneChip RNA profiling data analysis and validation project using one
of the most comprehensive human testicular expression data sets available, in combination with the
output of a very large GeneChip RNA profiling study including a wide variety of human somatic
cancers (Expression Project for Oncology, expO; www.intgen.org), and a large number of
corresponding somatic healthy control samples (Gene Omnibus). Our in silico screen identified
numerous known CT antigens, genes that were previously associated with cancer progression, and
many as yet poorly characterized genes. We now wish to confirm and extend the observed RNA
patterns. For IQUB and FAM71B, we propose to validate the RNA profiles at the protein level using
commercialized reagents. The reagents will be used to monitor protein levels using testicular sections,
cultured cells, and commercially available tissue microarrays (TMAs) that contain a large number of
cancer samples and corresponding healthy controls. The proposed work will characterize novel target
proteins that we plan to further study and exploit in follow-up work in collaboration with InsermTransfert (Inserm’s patenting office), and experts in the field of immunotherapy, who are meant to
assess the potential clinical impact of novel CT antigens.
Techniques mises en œuvre par le stagiaire : Protein detection by Western blotting,
immunofluorescence (IF) and immunohistochemistry (IHC). Protein extraction (Western), cell culture,
tissue sectioning (IF, IHC). Light/UV microscopy (Zeiss). Knowledge mining using databases (neXtProt,
Human Protein Atlas, Genevestigator, TIMER, GermOnline).
Publications du Responsable de stage au cours des 5 dernières années :
The protein expression landscape of mitosis and meiosis in diploid budding yeast. Becker E, Com E,
Lavigne R, Guilleux MH, Evrard B, Pineau C, Primig M. J Proteomics. 2017 Mar 6;156:5-19.
Ndt80 activates the meiotic ORC1 transcript isoform and SMA2 via a bi-directional middle sporulation
element in Saccharomyces cerevisiae. Xie B, Horecka J, Chu A, Davis RW, Becker E, Primig M. RNA
Biol. 2016 Sep;13(9):772-82.
The epigenetic processes of meiosis in male mice are broadly affected by the widely used herbicide
atrazine. Gely-Pernot A, Hao C, Becker E, Stuparevic I, Kervarrec C, Chalmel F, Primig M, Jégou B,
Smagulova F. BMC Genomics. 2015 Oct 30;16:885.
Global alterations of the transcriptional landscape during yeast growth and development in the
absence of Ume6-dependent chromatin modification. Lardenois A, Becker E, Walther T, Law MJ, Xie
B, Demougin P, Strich R, Primig M. Mol Genet Genomics. 2015 Oct;290(5):2031-46.
The BioMart community portal: an innovative alternative to large, centralized data repositories.
Smedley D, et al. Nucleic Acids Res. 2015 Jul 1;43(W1):W589-98.
The histone deacetylase Rpd3/Sin3/Ume6 complex represses an acetate-inducible isoform of VTH2 in
fermenting budding yeast cells. Stuparevic I, Becker E, Law MJ, Primig M. FEBS Lett. 2015 Apr
2;589(8):924-32.
The conserved histone deacetylase Rpd3 and the DNA binding regulator Ume6 repress BOI1's
meiotic transcript isoform during vegetative growth in Saccharomyces cerevisiae.
Liu Y, Stuparevic I, Xie B, Becker E, Law MJ, Primig M. Mol Microbiol. 2015 May;96(4):861-74.
Erratum in: Mol Microbiol. 2016 Jan;99(1):217.
Integrated RNA- and protein profiling of fermentation and respiration in diploid budding yeast provides
insight into nutrient control of cell growth and development. Becker E, Liu Y, Lardenois A, Walther T,
Horecka J, Stuparevic I, Law MJ, Lavigne R, Evrard B, Demougin P, Riffle M, Strich R, Davis RW,
Pineau C, Primig M. J Proteomics. 2015 Apr 24;119:30-44.
Combining RNA and protein profiling data with network interactions identifies genes associated with
spermatogenesis in mouse and human. Petit FG, Kervarrec C, Jamin SP, Smagulova F, Hao C,
Becker E, Jégou B, Chalmel F, Primig M. Biol Reprod. 2015 Mar;92(3):71.
The conserved histone deacetylase Rpd3 and its DNA binding subunit Ume6 control dynamic
transcript architecture during mitotic growth and meiotic development. Lardenois A, Stuparevic I, Liu Y,
Law MJ, Becker E, Smagulova F, Waern K, Guilleux MH, Horecka J, Chu A, Kervarrec C, Strich R,
Snyder M, Davis RW, Steinmetz LM, Primig M. Nucleic Acids Res. 2015 Jan;43(1):115-28.
Developmental stage dependent metabolic regulation during meiotic differentiation in budding yeast.
Walther T, Létisse F, Peyriga L, Alkim C, Liu Y, Lardenois A, Martin-Yken H, Portais JC, Primig M,
François J. BMC Biol. 2014 Sep 2;12:60.
High-resolution profiling of novel transcribed regions during rat spermatogenesis. Chalmel F,
Lardenois A, Evrard B, Rolland AD, Sallou O, Dumargne MC, Coiffec I, Collin O, Primig M, Jégou B.
Biol Reprod. 2014 Jul;91(1):5.
Expression screening of cancer/testis genes in prostate cancer identifies NR6A1 as a novel marker of
disease progression and aggressiveness. Mathieu R, Evrard B, Fromont G, Rioux-Leclercq N, Godet J,
Cathelineau X, Guillé F, Primig M, Chalmel F. Prostate. 2013 Jul;73(10):1103-14.
Genome-wide identification of Sox8-, and Sox9-dependent genes during early post-natal testis
development in the mouse. Chalmel F, Lardenois A, Georg I, Barrionuevo F, Demougin P, Jégou B,
Scherer G, Primig M. Andrology. 2013 Mar;1(2):281-92.
Transcription of two long noncoding RNAs mediates mating-type control of gametogenesis in budding
yeast. van Werven FJ, Neuert G, Hendrick N, Lardenois A, Buratowski S, van Oudenaarden A, Primig
M, Amon A. Cell. 2012 Sep 14;150(6):1170-81.
Global human tissue profiling and protein network analysis reveals distinct levels of transcriptional
germline-specificity and identifies target genes for male infertility. Chalmel F, Lardenois A, Evrard B,
Mathieu R, Feig C, Demougin P, Gattiker A, Schulze W, Jégou B, Kirchhoff C, Primig M. Hum Reprod.
2012 Nov;27(11):3233-48.
The bioinformatics tool box for reproductive biology. Primig M. Biochim Biophys Acta. 2012
Dec;1822(12):1880-95.
GPSy: a cross-species gene prioritization system for conserved biological processes--application in
male gamete development. Britto R, Sallou O, Collin O, Michaux G, Primig M, Chalmel F. Nucleic
Acids Res. 2012 Jul;40(Web Server issue):W458-65.
Autres informations:
Etudiants actuellement en thèse ou en M2 dans l’équipe d’accueil. Pour chaque étudiant indiquez
le nom du responsable de thèse, l’année du début de la thèse et l’Ecole Doctorale de rattachement
2015-2018: Yvan Dietrich, C. Pineau, MATISSE, France
2013-2017: Karolina Modzelewska, C. Pineau, UR1 VAS, France
2014-2017: Loren Méar, C. Pineau, François Vialard, GAO, UVSQ, France
Etudiants ayant préparé ou soutenu leur thèse ou leur M2 dans l’équipe d’accueil au cours des
six dernières années.
PhD
2014-2016: Bingning Xie, M. Primig, UR1 VAS, postdoctoral researcher, China
2014-2016: Chunxiang Hao, M. Primig, F. Smagulova, UR1 VAS, lecturer Linyi University, Linyi, China
2011-2014: Sophie Chocu, C. Pineau, UR1 VAS, teacher, France
2012-2014: Lauriane Sedès, S. Jamin, X, Univ. Paris-Sud (ED419), postdoctoral researcher, France
2008-2001: Yuchen Liu, Primig, UR1 VAS, lecturer at Jianghan University, Wuhan, China
2008-2011: Ramona Britto, M. Primig, UR1 VAS, bioinformaticist, EBI, Hinxton, UK
2009-2012: Thomas Freour, C. Pineau, D. Masson, UR1, VAS, chef de service CECOS, CHU Nantes
M2
2015: Aline Castellier, C. Pineau, M. Lagarrigue, UR1, France
2014: Huong Do, M. Primig, UR1, France.
2014: Stephane Dinanet, C. Pineau, N. Melaine, M. Lagarrigue, R. Lavigne, UR1, France.
2011: Ludovic Chaillet, C. Pineau, M. Lagarrigue, UR1, France
2011: Romain Mathieu: F. Chalmel and M. Primig, CHU Rennes, France
2011: Marie-Charlotte Dumargne, F. Chalmel and M. Primig, UR1, France
2010 : Nolwen Hernio, C. Pineau, UR1, France
Cette proposition de stage s’adresse-t-elle spécifiquement à un étudiant scientifique, médecin
ou vétérinaire ou bien est-il ouvert à tous les profils ? Scientifique, médecin
Ce sujet peut-il donner lieu à une thèse ? OUI