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The role of PQM-1 in proteostasis and transcellular chaperone signalling

O'Brien, Daniel Thomas (2019) The role of PQM-1 in proteostasis and transcellular chaperone signalling. PhD thesis, University of Leeds.

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O'Brien_DT_MolecularandCellularBiology_PhD_2019.pdf - Final eThesis - complete (pdf)
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C. elegans are free living nematodes which are well placed as a model organism for the heat shock response. I have investigated the zinc finger transcription factor PQM-1 to discern its function in both acute heat stresses and long term suppression of aggregation prone proteins. I found that PQM-1 is required for C. elegans heat stress survival and that its presence helps suppress the aggregation of polyglutamine rich proteins. I followed this result up with an appraisal of the transcriptome of C. elegans during heat stress, in the presence and absence of pqm-1 to ascertain which genes were regulated by PQM-1 during heat stress. I also investigated the localisation and regulation of PQM-1 in heat stress conditions and found that the abundance of the protein and its subcellular localisation is influenced by both the ubiquitin ligase uba-1, and the kinase sgk-1. As a result of my studies I have discovered a novel role for PQM-1 in the heat shock response, and that it is required for proteostasis maintenance as the organism ages. Furthermore, I have also determined that a specific transcriptional programme is regulated by PQM-1 post-heat stress and identified several proteins that PQM-1 interacts with under these conditions.

Item Type: Thesis (PhD)
Keywords: PQM-1, proteostasis, C. elegans, transcellular chaperone signalling, heat shock
Academic Units: The University of Leeds > Faculty of Biological Sciences (Leeds) > Institute for Molecular and Cellular Biology (Leeds)
Depositing User: Mr Daniel T O'Brien
Date Deposited: 28 Jan 2020 11:48
Last Modified: 28 Jan 2020 11:48
URI: http://etheses.whiterose.ac.uk/id/eprint/25808

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