Andrew Kil
Pronouns: He/Him
Research Mentor(s): Ravi Allada
Research Mentor School/College/Department: Anesthesiology/MNI / Medicine
Program:
Authors: Andrew Kil, Yong-Kyu Kim, Ravi Allada
Session: Session 7: 4:40 pm – 5:30 pm
Poster: 32
Abstract
Traumatic brain injury (TBI) is a major cause of mortality, constituting approximately 30% of all injury-related deaths in the United States (Taylor et al. 2017). After initial injury, TBI patients undergo lasting neurodegeneration (secondary injury), but due to the complexity of TBI mechanisms, treatments have stalled (Katzenberger et al. 2013). Nearly 75% of human genes have a fly ortholog, making Drosophila melanogaster an ideal model organism (Buhlman et al. 2021). The Allada lab seeks to identify candidate genes and pathways in a novel Drosophila model of TBI by delivering an estimated force of 8.8 Newton to a fly head using the dCHI system, being highly replicable (van Alphen et al. 2022). TRAP-seq analysis shows 500 genes underwent TBI-induced changes in gene expression. Using RNA interference methods, we knocked down these individual genes and evaluated the 150 most promising candidates. We crossed the males of RNAi lines to Repo-Gal4 females. The F1 males were collected and subjected to TBI. TBI flies were then tested for 24h mortality, climbing activity, and sleep. For sleep analysis, 16 F1 males were loaded in behavioral tubes of the DAM system, which recorded sleep behavior for 12 days in a 5LD:7DD cycle. Non-dCHI (sham) flies were used as controls. The TBI-induced flies showed greater mortality, reduced climbing activity, and decreased sleep behavior compared to sham flies. After screening the 150 candidate genes, we identified 25 genes significantly reducing mortality, 5 genes improving climbing activity, and 5 genes increasing sleep behavior. After conducting validation experiments on these genes using secondary RNAi lines, we found that 7 candidate genes significantly reduced 24h mortality, while 0 candidate genes were found to have improved climbing activity or sleep behavior. These results will inform future testing of FDA-approved drugs on the Drosophila model, providing positive social benefits.
