Laboratoires, pour proposer une thématique de

recherche partenariale soutenue par le dispositif CIFRE, merci de remplir les

champs suivants, et d’envoyer le document à : cifre@anrt.asso.fr

● Nom du laboratoire : U1163/Institut Imagine Laboratoire d'homéostasie normale et pathologique

du système immunitaire

● Ville et code postal : Paris 75015

● Numéro de reconnaissance : UMR1163

● Etablissement d’appartenance INSERM

● Candidat déjà sélectionné : OUI NON

● Descriptif de la thématique de recherche (sans aucun caractère confidentiel) :

New molecular effectors regulating stimulus-secretion coupling in mast cells in allergy

Mast cells (MC) have long been recognized for their detrimental roles in allergic diseases such as
allergic rhinitis, asthma, food allergies, or urticaria, which affect almost one third of the people in
western countries. MC are tissue-localized cells of hematopoietic origin. They survey their
environment and combat infectious and parasitic agents by releasing a whole variety of inflammatory
mediators after degranulation or by new synthesis of different cytokines and chemokines. These
mediators rapidly initiate tissue responses such as the well-known vasoactive actions of histamine. In
the long-term the release of chemokines and cytokines stimulate the attraction of other immune
effector cells and contribute to immunoregulatory processes. Release occurs in response to many
stimuli (Fc receptors, GPCRs, TLRs, cytokine receptors etc). While in the past, studies for therapeutic
intervention have mostly focused on individual receptor; the IgE receptor (FcRI), it has become clear
that multiple receptors become activated during an inflammatory response calling for novel
approaches acting at late secretion steps. The goal of this PhD project is to better understand the
molecular mechanisms regulating the late signaling events of vesicular trafficking leading to pre- and
neoformed mediator release by MC. This will not only provide new insights into MC biology but will
also offer a real opportunity to identify novel therapeutic targets. To this end, we propose a whole
cell proteomic approach coupled to high-throughput siRNA screening to identify new specific
effectors of MC degranulation and CCL2 secretion, which will be studied further functionally and in
preclinical models.

● Disciplines de la thématique de recherche :

01. Département Mathématiques et leurs 06. Département Sciences humaines et

interactions humanités

02. Département Physique 07. Département Sciences de la société

03. Département Sciences de la terre et de 08. Département Sciences pour l’ingénieur

l’univers, espace
 04. Département Chimie Matériaux 09. Département Sciences et technologies de
l’information et de la communication

05. Département Biologie, médecine et santé 10. Département Sciences agronomiques et

écologiques

● Date de démarrage souhaitée : octobre 2017

● Contact mail : gael.menasche@inserm.fr

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