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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 (FcRI), 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.