Defense Date

2021

Document Type

Thesis

Degree Name

Master of Science

Department

Human and Molecular Genetics

First Advisor

Michael Grotewiel

Abstract

Alcohol use disorder is a global public health issue that affects millions across the world. It can result in negative physical and mental health outcomes, and currently treatment options are limited and rates of relapse are high. Identifying genes that affect aspects of ethanol behaviors in model organisms, such as Drosophila melanogaster, can serve to eventually develop more robust therapeutic interventions for those experiencing alcohol dependence. Previous studies have identified a relationship between a person's initial sensitivity to alcohol and their abuse potential for the drug in later life. Therefore, we can study sedation behaviors in Drosophila melanogaster to better understand genes that affect alcohol sensitivity. Work in the Grotewiel laboratory has identified the gene Mef2 as a key regulator of ethanol sedation. The major goals of these studies were to identify genes downstream of Mef2 that produce a consistent behavioral impact on sedation when knocked down (Chapter 2) and to identify global gene expression changes resulting from Mef2 knockdown (Chapter 3). We found that RNAi transgenes against two genes, spin and unc79 consistently and significantly increase sedation time upon exposure to ethanol. Though RNA-seq studies, we identified several Mef2 dependent differentially expressed candidates for future studies in ethanol sedation. we compared whether these differentially expressed genes had a significant overlap with genes previously known to bind Mef2. Overall, the studies in this thesis support several novel hypotheses regarding the role of Mef2 and its downstream genes in ethanol sedation that can be explored in the future.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

8-11-2021

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