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Title: Maintenance of genetic and physiological stability in Caenorhabditis elegans
Author: Chen, Yannic
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2020
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The genetic and physiological stability of an organism is essential to ensure its well-being and survival. This project investigates the effect of epigenetic changes on genetic stability, and the association between different stressors that threaten the physiological stability of C. elegans. Part 1: Gene expression is controlled by epigenetic effects such as DNA methylation and histone modification. The histone modification H3K4me3 is associated with actively transcribed genes and co-localizes with a DNA:RNA hybrid structure known as R-loops which are associated with DNA instability. To investigate the link between H3K4me3 and R-loops, I use Caenorhabditis elegans COMPASS mutants set-2(bn129) and cfp-1(tm6369), that have drastically reduced global H3K4me3 marks. I found that set-2(bn129) has a consistent reduction of R-loop levels compared to wild-type worms, suggesting that SET-2 (or H3K4me3) is vital in sustaining the R-loop levels observed in wild-type worms. Furthermore, seven helicases have been identified to rescue the R-loop levels in set-2(bn129) mutants, four of which are chromatin remodelers, suggesting a link between chromatin remodelling and R-loop aggregation. Part 2: Environmental stress is a common influence that threatens the health of an organism. While different stressors elicit different responses, how these different responses are interconnected is not well understood. To investigate this, I use a bioinformatic approach to compare the response of C. elegans under heat stress and biotic stress inflicted by pathogen infection. Comparison of transcriptomic data from C. elegans infected by different pathogens indicates an overall dissimilar gene expression response. However, a small set of “general pathogen responsive genes” are consistently differentially expressed at a low level under most pathogen infections. Comparing these general pathogen responsive genes with heat shock responsive genes identified a significant overlap of 50 genes. This suggests that the heat shock response and innate immune response partially overlap.
Supervisor: Westhead, David R. ; van Oosten-Hawle, Patricija Sponsor: University of Leeds
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available