OBJECTIVES
1. Identification of factors involved in IL-1β secretion and aggregation
2. Discovery of GRASP55-dependent functional intermediates controlling IRE1α activity
3. Assess the involvement of GRASP55-IRE1α axis in α-synuclein physiology
RESUTLS
Implementation of this project should have as outcome:
- deciphering the mechanism of GRASP55-dependent IRE-1α activation
- identify intermediates of the stress sensing machinery to induce cytoplasmic proteome instability.
- to identify the key proteins involved in UPS cargo aggregation, potential targets to control the secretion of cytoplasmic proteins in the context of inflammation and neurodegeneration.
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2021:
-We have analysed by mass spectrometry the composition of the IL-1β-containig aggregates in primary macrophages
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2022:
-We have identified and validated some of the targets identified in the previous aim to be involved in GRASP55-dependent protein aggregation in macrophages
-We successfully applied the CRISPR/Cas9 knock-in technology to generate an endogenously tagged cell line
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2023:
-We evaluated the cross-species conservation of the GRASP55-IRE-1α axis in an animal model (C. elegans)
-We investigated the involvement of the GRASP55-IRE-1α axis in synuclein aggregation both using neuronal cells and animal model engineered to express human synuclein.
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