[Fellowship] Plasma cell Regulation and IgE Survival Mechanisms
Ente: Horizon Europe Guarantee
Scadenza: 2026-05-31
Paese: GB
Descrizione
Allergies have been rapidly worsening in recent decades, becoming the most common chronic disease in Europe to date. While some allergic reactions are mild, a severe reaction can lead to anaphylaxis and death. Yet, even mild reactions cause distress, discomfort, and a fair amount of disability to the patients, leading to lost time from school and work. Hence, allergies are a wide-scale problem as they pose an increasing burden to the European and worldwide health care systems and economy.
The main culprit behind many allergic symptoms is the dysregulated production of allergen-specific immunoglobulin E (IgE) antibodies by plasma cells (PCs). In contrast to IgG1 responses, healthy IgE responses are normally low and transient, suggesting the existence of a fundamental difference in the regulation of IgE cells. Despite its importance in health and disease, the precise mechanisms regulating the apoptosis or survival of IgE plasma cells remain poorly characterised. We hypothesise that the survival differences observed between IgG and IgE PCs are due to the unique signalling signature of the IgE B cell receptor (BCR), potentially via calcium signalling. We also hypothesise that IgE PCs might have increased levels of ER stress, triggering a terminal Unfolded Protein Response (UPR) and apoptosis. The failure of such suppressive mechanisms in response to allergens might contribute to allergic disease. PRISM is a multidisciplinary project that will combine the researcher's experience in immune cell biology and advanced microscopy with the supervisor's renowned expertise in B cell receptor signalling and CRISPR genetic manipulation to uncover the molecular mechanisms underlying the generation and survival of IgE plasma cells. Understanding the intricacies of plasma cell biology can pave the way for pioneering therapeutic approaches, not limited to allergy but also extending to other PC- related diseases.
Settori: Infection
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