Date of Award

10-11-2024

Publication Type

Thesis

Degree Name

M.Sc.

Department

Biological Sciences

Keywords

epigenetics;foraging;G9a;nociception

Supervisor

Jeffrey Dason

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Abstract

The Drosophila melanogaster foraging gene encodes a cyclic guanosine monophosphate (cGMP)-dependent protein kinase G (PKG) that regulates nociception. Furthermore, PKG expression is increased in nerve injury-induced nociceptive hypersensitivity mouse models. It is unknown whether foraging expression changes in response to injury in Drosophila. Additionally, the mechanisms by which PKG expression are regulated in response to injury remains elusive. The histone methyltransferase G9a has previously been shown to regulate foraging mRNA expression, and higher foraging levels were previously found to cause nociceptive hypersensitivity, whereas loss of foraging reduced nociceptive sensitivity. However, a direct link between foraging and G9a with respect to nociception has not been established. I found that G9a null mutants displayed nociceptive hypersensitivity in comparison to their genetic control. Protein analysis determined that FORAGING protein levels are increased in the absence of G9a, specifically, the FORAGING P1 isoform expression was upregulated in G9a null mutants. Examination of G9a foraging null double mutants demonstrated that G9a likely functions upstream of foraging in regulating nociception. Compared to control genotypes, overexpression of FORAGING resulted in significantly faster nociceptive response latencies. Furthermore, ultraviolet (UV) injury induced a nociceptive hypersensitive response in control genotypes. However, this injury-induced nociceptive hypersensitivity was blocked in the absence of foraging. Collectively, my findings demonstrate that G9a negatively regulates nociception and FORAGING P1 protein expression.

Available for download on Thursday, October 09, 2025

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