Project description
New insights into mast cell biology
Mast cells are tissue-resident immune cells involved in allergy, cancer and neurodegeneration. They exert their immune responses through the release of secretory granules (SGs), which contain protective and pro-inflammatory mediators. Recent evidence suggests that mitochondrial and endoplasmic reticulum (ER) proteins are also secreted during this process. This observation suggests a previously unknown metabolic role for SGs, potentially linked to a selective degradation pathway for ER components. With the support of the Marie Skłodowska-Curie Actions programme, the CrossMastER project aims to elucidate the underlying mechanisms of this SG-ER relationship. Researchers will utilise super-resolution microscopy techniques to study mast cell biology, paving the way for the identification of novel drug targets that modulate immune responses in disease.
Objective
Mast cells (MCs) are tissue resident immune cells best known for their role in allergy. However, as part of the adaptive and innate immune system they engage in various pathologies including cancer and neurodegeneration. When MCs exert their immune response, special lysosome-related organelles, called secretory granules (SG), in which protective and proinflammatory mediators are prestored, undergo exocytosis. The recent discovery that during this process also mitochondrial and endoplasmic reticulum (ER) proteins are secreted, suggests that SGs may have, in addition to their extracellular immune, an intracellular metabolic function, such as in mito- or ER-phagy. In preliminary work using ultra expansion microscopy (uExM) we indeed found that the ER-phagy receptor SEC62 also localizes to the SG lumen. Strikingly, we further discovered that the exocytosis of SGs is accompanied by drastic ER-remodelling, particularly peripheral ER-sheet formation.
However, the biological purpose as well as the underlying mechanism of this process and whether ER-phagy may be involved is currently unclear. Further, it remains to be elucidated which of the three ER-phagic pathways (macro-, micro-ER-phagy, LC3-dependent vesicular transport) connects to the SGs and whether the fate of the resulting vesicle represents a way of unconventional protein secretion.
Due to the size of ER membranes, the sub-vesicular/ER-phagic structures and the densely filled MC cytoplasm, the investigation of the assembly and evolution of SG-ER contacts demands a look beyond the diffraction limit of light. Therefore, I will employ different super-resolution methods such as uExM and live cell Stimulated Emission Depletion (STED) microscopy in combination with automated image analysis, to answer these questions.
This work will advance our understanding of the unique cell biology of MCs and the formation and release of their SGs giving rise to new drug targets to modulate MC immune responses in health and disease.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy
- medical and health sciences clinical medicine oncology
- medical and health sciences clinical medicine allergology
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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(opens in new window) HORIZON-MSCA-2025-PF
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14195 Berlin
Germany
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