Multi Omics integration to decipher IRE1 signalling in pathologies

Inositol-requiring enzyme 1 (IRE1) is a central regulator of the unfolded protein response (UPR) and the most evolutionarily conserved endoplasmic reticulum (ER) stress sensor among eukaryotes. Upon activation, IRE1 transmits stress signals through two principal effector pathways: the splicing of XBP1 mRNA and the Regulated IRE1-Dependent Decay (RIDD) of RNAs. Together, these branches initially act to restore proteostasis, but under chronic stress they can promote pathological processes such as inflammation, apoptosis, and metastasis. Owing to its central role, dysregulated IRE1 signalling contributes to a broad spectrum of diseases, including metabolic disorders, neurodegeneration, and cancer. This thesis addresses IRE1 signalling in disease through a dual-faceted approach: (1) the development of computational tools for multi-omics integration and biomarker discovery, and (2) their application to both publicly available and in-house generated datasets.

Publisher

University of Galway

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CC BY-NC-ND

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University of Galway Theses (PhD Theses)