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dc.contributor.authorWang, Chi-Fongen_US
dc.date.accessioned2015-08-05T04:25:12Z
dc.date.available2015-08-05T04:25:12Z
dc.date.issued2012
dc.date.submitted2012
dc.identifier.other(ALMA)contemp
dc.identifier.urihttps://hdl.handle.net/2144/12667
dc.descriptionThesis (M.A.)--Boston University PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.en_US
dc.description.abstractProtein folding is a fundamental function of the cell, and chaperone proteins are essential to ensure the quality of secretory and membrane-bound proteins leaving the endoplasmic reticulum (ER). In eukaryotic cells, an increase in translational load that exceeds the capacity of chaperone proteins results in the accumulation of misfolded proteins in the ER, a condition termed ER stress. A network of signaling pathways, known as the Unfolded Protein Response (UPR), senses and responds to ER stress by globally decreasing translational load, specifically increasing expression of chaperone proteins, and expanding the ER lumen. In metazoans the UPR is mediated through three signaling pathways: IRE-1, PEK-1, and ATF-6. The IRE-1 branch of the UPR is highly conserved and found in all eukaryotic cells, from yeast to mammals. Previous work has shown that XBP-1, a transcription factor activated by IRE-1, plays a critical role in the survival of Caenorhabditis elegans worms on pathogenic Pseudomonas aeruginosa bacteria by protecting the animal from excessive ER stress induced by immune activation (Richardson et al., 2010). XBP-1 also contributes to the maintenance of ER homeostasis, as mutant worms lacking XBP-1 exhibit constitutively elevated ER stress (Richardson et al., 2011). Our goal was to explore and identify novel genes that interact with the IRE-1/XBP-1 branch of the UPR. This was done by studying worms lacking XBP-1 and possessing mutations that suppressed immune-induced larval lethality and other XBP-1 loss-of-function phenotypes, presumably through some compensatory mechanism(s). ER stress was induced by four distinct methods (growth on pathogenic bacteria, tunicamycin treatment, heat stress, and removal of the PEK-1 branch of the UPR). This study yielded promising preliminary results for the regulation of XBP-1. The tunicamycin treatment identified probable suppressors of basal ER stress specifically, not just immune-induced lethality. The heat-stress results support a correlation between temperature and UPR induction, a relationship which currently remains unclear. Our data also suggest that PEK-1 has a compensatory role in the absence of XBP-1, although this awaits confirmation that it is independent of functional RNAi machinery. More work is needed to identify the genes responsible for alleviating ER stress and to further understand the complex regulation of the UPR.en_US
dc.language.isoen_US
dc.publisherBoston Universityen_US
dc.titleGenetic analysis of the unfolded protein response in Caenorhabditis elegans physiology and immunityen_US
dc.typeThesis/Dissertationen_US
etd.degree.nameMaster of Artsen_US
etd.degree.levelmastersen_US
etd.degree.disciplineMedical Sciencesen_US
etd.degree.grantorBoston Universityen_US


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