Document Type
Conference Paper
Publication Date
8-24-2025
Publication Source
Proceedings of the 2025 Berry Summer Thesis Institute
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in several hundred million contracted cases of coronavirus disease 2019 (COVID-19) and a global pandemic. In some of these cases, previous neurological diseases, such as Alzheimer’s disease (AD), seemed to progress much more rapidly after the COVID-19 infection. Thus, we became interested in studying the effects of SARS-CoV-2 infection on prior neurological disease progressions.
To modulate this condition, we used Drosophila melanogaster as a genetic model system. We had previously developed the Alzheimer’s Disease Fly Model with expression of human amyloid beta 42 (Aβ42) peptide, which is responsible for extracellular Aβ-42 plaque deposition. This model is crucial in understanding how SARS-CoV-2 impacts neurodegenerative disorders.
Our lab conducted a screening of different SARS-CoV-2 coat proteins to mis-express in the fly eye and scored for the phenotypes. We mis-express these proteins using a Gal4-upstream activating sequence (Gal4-UAS) system, which keeps the downstream gene dormant in its host fly until it is crossed with a fly expressing the necessary Gal4 for activating the transcription of the downstream gene of interest. This will allow for the controlled expression of the SARS-CoV-2 proteins under a tissue-specific promoter. In the screening, we identified two proteins of interest: nonstructural protein 6 (Nsp6) and an accessory protein, open reading frame 7a (Orf7a).
To understand how these proteins contribute to worsening neurodegeneration. I propose two aims:
- To check the phenotypes of Nsp6 and Orf7a in the background of Aβ42 flies.
- To check the effect of observed phenotypes under developmental stages and conduct the immuno-histochemistry experiments to check levels of the mis-expressed proteins.
By the conclusion of the Berry Summer Thesis Institute program, I aim to understand the neurological impact of Nsp6 and Orf7a, including possible effects on neurodegeneration.
Keywords
SARS-CoV-2, COVID-19, Alzheimer's, Nsp6, Orf7a, Aβ-42, Gal4-UAS, Immunohistochemistry
Disciplines
Genetics | Immunology of Infectious Disease | Respiratory Tract Diseases
Sponsoring Agency
Berry Summer Thesis Institute, Berry Family Foundation
eCommons Citation
Huettemann, Jeffrey William and Singh, Amit, "Crossroads of COVID-19 and Alzheimer’s: Investigating SARS-CoV-2 Nsp6 and Orf7a in Amyloid-β42 Toxicity" (2025). Proceedings of the Berry Summer Thesis Institute, 2025. 3.
https://ecommons.udayton.edu/uhp_bsti_2025/3
Included in
Genetics Commons, Immunology of Infectious Disease Commons, Respiratory Tract Diseases Commons
Comments
Acknowledgments: I would like to express my sincerest gratitude to Dr. Amit Singh, Sunanda Yogi, and all others in my lab for assisting me in my research this summer. Additionally, I would also like to thank the Honors Program, the Berry family, and especially Dr. Dorian Borbonus for enabling my research this summer through the Berry Summer Thesis Institute. Through the Berry Summer Thesis, I have acquired a wide range of techniques and skills that will prepare me for future research endeavors. Without those who have been mentioned, the research undertaken this summer would not have been possible.