O'Brien, Daniel Thomas (2019) The role of PQM-1 in proteostasis and transcellular chaperone signalling. PhD thesis, University of Leeds.
Abstract
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.
Metadata
Supervisors: | van Oosten-Hawle, Patricija and Westhead, David |
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Keywords: | PQM-1, proteostasis, C. elegans, transcellular chaperone signalling, heat shock |
Awarding institution: | University of Leeds |
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: | 01 Feb 2025 01:05 |
Open Archives Initiative ID (OAI ID): | oai:etheses.whiterose.ac.uk:25808 |
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