The Application of Fruit Flies in Studying Human Neurodegenerative Diseases
Summer Gibson*, Ranah Ocampo*, Adam Davis, and Jo Qian 3820 Mundy Mill Rd, University of North Georgia, Oakwood, GA 30566
The intracellular transport of diverse cargoes, such as organelles, from one end of the axon to the other, is crucial for the survival, development, and function of a neuron. Disturbances in axonal transport are key pathological events that contribute to many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). Fruit fly (Drosophila melanogaster) is commonly used as a model organism to address mechanisms of human neurodegenerative diseases, due to the highly conserved genome between flies and humans and the simplicity of fly nervous system compared to that of humans. In this project, we focused on the fruit fly gene p150glued, which is a homolog of the human gene DCTN1. P150glued encodes the major subunit of dynactin, a protein complex that functions in intracellular transport. We performed bioinformatics studies by analyzing amino acid sequences of p150glued between various model organisms. We identified the conserved amino terminal cytoskeleton-associated protein glycine-rich (CAP-Gly) microtubule-binding domain of p150Glued and found a number of disease-associated amino acid variants present in that domain. In addition, we performed antibody staining and immunofluorescence microscopy to visualize axonal transport in flies. We found the loss-of-function mutation of p150glued disrupted the process of axonal transport in third-instar larvae. This project provides several learning outcomes for students, including the identification of conserved protein domains and functional sites on amino acid sequences, mastery of microdissection and imaging of subcellular protein localization, and a greater comprehension of the pathogenesis of neurodegenerative diseases.