Subject Area
Biological Sciences, General
Abstract
The underlying molecular processes of aberrant protein expression in neurodegeneration are intricate and multifaceted, with ribosome-associated quality control (RQC) emerging as a promising avenue of exploration. Ribosome-associated quality control is integral to cellular function. Its evolutionarily conserved pathway encompasses a network of mechanisms designed to ensure the fidelity of protein synthesis, folding, and degradation within the cells of all eukaryotes. The ribosome, central to protein synthesis, plays a pivotal role in this quality control network, and its malfunction can lead to the accumulation of misfolded or aberrant proteins. In the context of neurodegenerative disorders, this dysfunction can have dire consequences. Protein misfolding and aggregation are common features in neurodegenerative diseases, and ribosome-associated quality control is critical in preventing or mitigating these events. Therefore, dysfunction in ribosome-associated quality control mechanisms is not merely a consequence of neurodegenerative disorders; it may also be a driving force, creating a feedback loop that exacerbates protein homeostasis failure.
This study aims to investigate the potential role of ribosome-associated quality control in Drosophila models in the context of neurodegenerative diseases and cellular stress. In Chapter 1, we established a protocol for the construction of a high-throughput method to induce traumatic brain injury in D. Melanogaster. In Chapter 2, we investigated the role of TDP-43 ribonuclear protein in the rescue of mitochondrial morphology in PINK1 mutant models. Chapter 3 aims to determine the effects of Usp10/USP10 and rin/G3BP1 overexpression and knockdown under drug-induced proteotoxic stress in aged flies. Finally, the appendix focuses on establishing baseline lifespan and histological data in transgenic fruit fly models of Batten Disease for future screenings of quality control proteins.
Degree Date
Spring 5-11-2024
Document Type
Thesis
Degree Name
M.S.
Department
Biological Sciences
Advisor
Zhihao Wu
Second Advisor
Richard Jones
Third Advisor
Adam Norris
Number of Pages
62
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Recommended Citation
Bonderer, Will, "SCREEN FOR BENEFICIAL GENETIC AND CHEMICAL MODIFIERS IN DROSOPHILA MODELS OF ALS AND TRAUMATIC BRAIN INJURY" (2024). Biological Sciences Theses and Dissertations. 26.
https://scholar.smu.edu/hum_sci_biologicalsciences_etds/26
