ITQB: CSD - PhD Theses
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- The role of Fbxo42 in Ataxin-2-mediated regulation of Xbp1 signallingPublication . Dias Santos, Cristiana Catarina; Domingos, Pedro"The accumulation of misfolded/unfolded proteins in the endoplasmic reticulum (ER) leads to a cellular condition known as “ER stress”. To alleviate this stress and restore cellular homeostasis, cells activate a signalling pathway collectively referred to as the Unfolded Protein Response (UPR). As a result, the ER sensor protein IRE1 is activated and mediates the splicing of XBP1 mRNA. Xbp1 spliced (Xbp1s) is an effective transcription factor and promotes the transcription of UPR-target genes, helping to reduce ER stress levels. However, when stress is prolonged or severe, it can lead to cell death by apoptosis.(...)"
- The molecular and organismal role of the EMCPublication . Gaspar, Catarina J.; Domingos, Pedro; Adrain, Colin"Integral membrane proteins (IMPs) comprise approximately 30% of the eukaryotic proteome and confer many essential functions to biological membranes. These proteins contain hydrophobic transmembrane domains (TMDs), which mainly populate the plasma membrane and the intracellular compartments of the secretory and endocytic pathways.(...)"
- Functional and genetic analysis of alpha-synuclein and huntingtin in Drosophila melanogasterPublication . Poças, Gonçalo; Domingos, PedroIn this work we established new transgenic Drosophila models for Parkinson’s (PD) and Huntington’s disease (HD), two incurable devastating human neurodegenerative diseases, which strongly compromise the patients’ motor abilities. Our Drosophila models are based on the transgenic overexpression of fluorescent-tagged versions of two human neuronal proteins extensively associated with these neuropathologies, but whose exact biological function is still unknown: alpha-synuclein (α-syn) for PD and huntingtin (Htt) for HD.(...)
- The Role of the Fbox Protein CG6758 in Xbp1s Induced Retinal Degeneration in DrosophilaPublication . Schweizer, Nadine; Domingos, PedroThe Unfolded Protein Response (UPR) is a signaling pathway that is activated by an accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) that causes ER stress. The activation of the UPR aims to restore ER homeostasis by attenuation of ER client protein translation, increased transcription of ER chaperones and ER associated degradation (ERAD) factors. If ER stress is too long or too strong, cells may die. The main signaling branch of the UPR is mediated by the ER transmembrane protein IRE1 and the transcription factor Xbp1. The active, spliced form of Xbp1 (Xbp1spliced) acts as a transcription factor with protective function against toxic protein aggregation. However, overexpression of Xbp1spliced in the developing Drosophila eye causes degeneration of the eye (“glossy” eye phenotype).(...)
- The Role of the Endoplasmic Reticulum Stress Transducer Ire1 during Photoreceptor Differentiation in DrosophilaPublication . Coelho, Dina Raquel da Silva; Domingos, PedroThe accumulation of misfolded proteins in the lumen of the endoplasmic reticulum (ER) causes ER stress and activates a homeostatic mechanism termed the Unfolded Protein Response (UPR). The most conserved arm of the UPR is mediated by the ER transmembrane protein Ire1 that removes an unconventional intron from Xbp1 mRNA upon ER stress. Xbp1spliced is an effective transcription factor that up-regulates ER chaperones and enzymes.(...)