Overview
This project investigates the relationship between bacteria-derived protein aggregates (BDPAs) and neurodegenerative disease pathogenesis using C. elegans as a model organism. Working in Dr. Daniel Czyż's lab at the University of Florida, I contributed to groundbreaking research examining how bacterial proteins influence host protein folding homeostasis.
Research Question
The work addresses a fundamental question in neurodegenerative disease research: how do gut bacteria contribute to protein misfolding and aggregation in the host? Understanding this relationship could reveal new therapeutic targets for diseases like Alzheimer's, Parkinson's, and ALS.
My Contributions
Time-Off-Pick (TOP) Assay Development
I developed and validated the Time-Off-Pick (TOP) assay, a novel phenotypic method for measuring motility impairments in C. elegans. This technique proved more inclusive than traditional swimming and crawling assays, particularly for strains with the roller phenotype.
- Designed experimental protocol using eyebrow hair picks
- Validated assay sensitivity across multiple C. elegans strains
- Demonstrated correlation with age-dependent motility changes
Protein Aggregate Quantification
I performed quantitative analysis of protein aggregates in Pseudomonas aeruginosa and other bacterial species using the ProteoStat fluorescence assay, establishing correlations between bacterial protein aggregate levels and their effects on polyglutamine aggregation in the worm intestine.
- Optimized ProteoStat assay for bacterial samples
- Quantified aggregates across multiple bacterial species
- Correlated BDPA levels with host proteostasis disruption
Key Findings
The research revealed that P. aeruginosa significantly induces polyQ aggregation in C. elegans, with the extent of aggregation directly proportional to the abundance of BDPAs. This work contributed to two peer-reviewed publications demonstrating that bacterial proteomes are not inert to host proteomes, and that disruption of bacterial proteostasis can affect host protein folding and potentially contribute to neurodegenerative diseases.
Impact & Publications
The findings suggest new therapeutic avenues targeting gut microbiota composition in patients with protein conformational diseases. This work resulted in two peer-reviewed publications:
- Bio-protocol (2022): Time-off-pick Assay to Measure Caenorhabditis elegans Motility
- International Journal of Molecular Sciences (2022): Bacteria-Derived Protein Aggregates Contribute to the Disruption of Host Proteostasis