master 2 immunologie - Faculté de médecine Paris Descartes

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MASTER 2 IMMUNOLOGIE
Send to Secrétariat Pédagogique du M2 d'Immunologie
[email protected]
2 pages maximum
Before June 1st 2016
Internship proposal for Master 2
(Proposition de Stage pour M2)
Academic Year 2016 - 2017
1. Team : administrative affiliation (CNRS, INSERM…) and number of the unit:
INSERM U1151
Name of the head of laboratory : X. Nassif
Name of the responsible of the team : P. van Endert
Name of the team : Présentation des antigènes : mécanismes et modulation par les
récepteurs Toll-like (équipe 9 INSERM U1151)
Adress : Hôpital Necker, 149 rue de Sèvres, 75015 Paris
Responsible for surpervising the student : E. Énée / P. van Endert
Tél ; Fax et E-mail: 01.44.49.25.63 / 01.44.49.53.82 ; [email protected]
2.
COURSE ( Parcours)
 Immunology
_ Physiopathologie de la réponse immune (Immunopathology)
3. Project : title and summary (Thème du stage, titre et Description du sujet) (1 page
maximum in english) :
Pancreatic beta cells constitutively up-regulate the unfolded protein response (UPR), a protective
cellular response with particular importance for cells subjected to high demand for secreted
proteins, for example pancreatic beta cells producing insulin. According to recent results, a lowlevel UPR not only protects beta cells by enhancing their capacity to fold, process and secrete
insulin, but also induces their proliferation. Our laboratory has discovered a novel mechanism
enhancing a protective UPR and beta cell proliferation. This mechanism is triggered by deletion of
an enzyme previously not linked to the UPR and results in protection of non-obese diabetic mice
from autoimmune diabetes. We propose a long-term four-year project with the final aim of
developing a new pharmacological approach for stimulation of beta cell proliferation. The objective
of this project, will be to first understand how deletion of the enzyme concerned triggers the UPR,
an objective we hope can be achieved during a master 2 internship. This will be achieved by
studying (pro)insulin synthesis, processing, trafficking and secretion in cells lacking the enzyme,
or treated with an available specific inhibitor. A second objective will be to understand how, in the
absence of the enzyme, inflammation becomes a signal triggering proliferation. In parallel, we will
undertake an open-ended search for signaling intermediates promoting proliferation, by coprecipitating proteins interacting with active and inactive enzyme, followed by mass-spectrometric
identification of proteins of interest. In the final stage of the project, we will analyze the effect of
enzyme inhibitors on beta cell proliferation in vivo, in preclinical models of autoimmune diabetes
and in recipients of islet grafts.
4. Composition of the team
Number of scientists :
Senior scientists :
Technician-Engineer :
Postdoc :
Total :
3
2
5
10
with HDR* :
3
Total HDR :
3
Number of students :
Master
1° Year of PhD :
2° Year of PhD:
3° Year of PhD :
4° Year of PhD :
Total PhD Students :
2
1
1
0
1
3
5. Publications (5 most significant during the 4 last years).
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Deprez-Poulain R, et al., Inhibition of insulin degrading enzyme by a small molecule induces glucose
intolerance. Nat Commun (2015) DOI: 10.1038/ncomms9250
-cells express a cathelicidin-related antimicrobial peptide regulating
autoimmune diabetes. Immunity 43 (2015): 304-17
Tenzer S, et al., HIV-1 adaptation to antigen processing results in population-level immune evasion and
affects subtype diversification. Cell Reports (2014), http://dx.doio.org/10.1016/j.celrep.2014.03.031
Parmentier N, et al., Insulin-degrading enzyme produces an antigenic peptide by degrading a cytosolic
protein. Nat. Immunol. 11 (2010): 449-54
Saveanu L, et al., IRAP identifies an endosomal compartment required for MHC class I crosspresentation. Science 325 (2009): 213-7
Membership of the Doctoral School (Appartenance à L’Ecole Doctorale)
BioSPC
B2T
 PPATH  Autre : ………
* Habilitation to supervise research