Research Symposium

BIO

Bethany Kear is a senior majoring in Cell and Molecular Neuroscience. This semester, she will be graduating summa cum laude with Honors in the Major and University Honors. Since 2023, she has investigated the link between neurofibromatosis and gut dysfunction as a member of the Brown Lab. She is a recipient of the Bess H. Ward Honors Thesis Award, which has provided funding for her project. Outside of school, Bethany volunteers with Big Bend Hospice and Tallahassee Memorial Hospital. After graduating, she will be applying to medical school.

Aging-dependent regulation of gene expression in a Drosophila model of Neurofibromatosis Type 1

Abstract

Neurofibromatosis type 1 (NF1) is a genetic disorder resulting from mutations in the Nf1 gene. NF1 affects 1 in 3000 people and presents with benign tumors of the peripheral nervous system, as well as dysregulation of sleep and metabolic rate. The fruit fly, Drosophila melanogaster, is an excellent genetic model to study NF1; flies with mutations in the Nf1 gene display decreased sleep and increased metabolic rate. Sleep loss has been associated with changes in gut homeostasis in both flies and mammals, and we previously found that selective knockdown of Nf1 in neurons of the brain increases gut permeability and reactive oxygen species (ROS) in the gut. This raises the possibility that loss of sleep contributes to gut dysregulation in this NF1 model. To explore the mechanisms that may underlie this link, we conducted an RNA-sequencing analysis of dissected gut tissue from control and Nf1 flies. We examined the gene expression of aged (20 days) Nf1 flies, young (5 days) Nf1 flies, and their aged-matched controls. Relative to controls, 32 genes were upregulated and 20 genes were downregulated in young Nf1 flies, while 15 genes were upregulated and 9 genes were downregulated in the aged condition. Future work will validate these candidate genes regulating sleep and gut homeostasis through genetic screening approaches. Overall, this work contributes to our understanding of the genetic basis of NF1 and its effect on gut health and physiology.

Keywords: Biology, Drosophila, Aging, Gut Health