Title

15. The Application of Fruit Flies in Studying Human Neurodegenerative Diseases

Faculty Mentor(s)

Jo Qian, PhD, Adam Davis, PhD

Campus

Gainesville

Proposal Type

Poster

Subject Area

Biology

Location

Nesbitt 3110

Start Date

25-3-2022 12:00 PM

End Date

25-3-2022 1:00 PM

Description/Abstract

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. 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 p150gluedbetween various model organisms. We identified the conserved aminoterminal cytoskeleton-associated protein glycine-rich (CAP-Gly) microtubule-binding domain of p150glued. We found a number of disease-associated amino acid variants present in that domain, which cause two distinct, nonoverlapping autosomal dominant neurodegenerative syndromes in humans, distal hereditary motor neuronopathy type VIIB (HMN7B) and Perry Syndrome. In addition, we performed antibody staining and immunofluorescence microscopy to visualize axonal transport in flies. We found the process of axonal transport was disrupted in the loss-of-function mutation of the p150glued third-instar larvae, possibly due to deadly traffic jams on neuronal highways. This project sheds light on the function of p150glued by revealing its potential role in the pathogenesis of neurodegenerative diseases

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Mar 25th, 12:00 PM Mar 25th, 1:00 PM

15. The Application of Fruit Flies in Studying Human Neurodegenerative Diseases

Nesbitt 3110

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. 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 p150gluedbetween various model organisms. We identified the conserved aminoterminal cytoskeleton-associated protein glycine-rich (CAP-Gly) microtubule-binding domain of p150glued. We found a number of disease-associated amino acid variants present in that domain, which cause two distinct, nonoverlapping autosomal dominant neurodegenerative syndromes in humans, distal hereditary motor neuronopathy type VIIB (HMN7B) and Perry Syndrome. In addition, we performed antibody staining and immunofluorescence microscopy to visualize axonal transport in flies. We found the process of axonal transport was disrupted in the loss-of-function mutation of the p150glued third-instar larvae, possibly due to deadly traffic jams on neuronal highways. This project sheds light on the function of p150glued by revealing its potential role in the pathogenesis of neurodegenerative diseases