Tucker Flynn, FCLC '28

Major: Integrative Neuroscience

Bio: Tucker Flynn is an undergraduate sophomore majoring in Integrative Neuroscience on a pre-health track. Tucker’s current research interests lie in the intersection between neurodegenerative disease and genetics, both of which he explored in his work with Dr. Jason Morris and Kyla Martin.

Title of Research: Molecular and Genetic Approaches to Studying the Intracellular Domain of Drosophila Presenilin

Mentor: Jason Morris, PhD, Natural Science

Research Partner: Kyla Martin

Abstract: Presenilin is the most often mutated gene in Familial Alzheimer’s Disease (FAD). This work establishes tools to study presenilin using Drosophila as an effective model organism. Mutations in human presenilin (PSEN) can cause familial Alzheimer’s disease by disrupting γ-secretase activity, but the mechanism by which it does so remains unclear, as does the role of specific protein regions. 

Drosophila Presenilin (Psn) has several varying lengths due to alternative splicing of exon 7. This region, exon 7, corresponds to a large cytoplasmic loop in the protein. There is a strong sequence similarity between the Drosophila and human sequences, except for exon 7. We identified two molecular approaches and one behavioral approach to study the structure and function of this region. We designed a plasmid encoding a guide RNA to generate an early stop codon in the long splice forms of Psn. Using flies with common pathogenic Psn mutations, we conducted a locomotor assay to determine whether this method can be used to analyze allele severity. Based on our preliminary results from the behavioral crawling assay, we suspect that WT larvae will crawl farther than Psn mutants. We require larger sample sizes and tightly timed egg lays to obtain statistically significant data.