Time-off-pick Assay to Measure Caenorhabditis elegans Motility

Walker, Alyssa C; Bhargava, Rohan; Brust, Amanda S; Owji, Ali A; Czyż, Daniel M.

doi:10.21769/bioprotoc.4436

Cited by 2 publications

(2 citation statements)

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“…We used our well-established and validated time-off-pick (TOP) assay that relies on C. elegans motility as a readout of proteotoxicity. 16,17 Consistent with their suppression of polyQ aggregation, all three strains alleviated aggregate-dependent motility defects with P. corporis having the strongest effect (Figure 3A, “Motility”). To determine whether the observed suppression is dependent on polyQ, we used N2 wild-type worms and a model expressing a shorter polyglutamine tract, polyQ33.…”

Section: Resultsmentioning

confidence: 60%

“…All motility assays were performed at room temperature as previously described. 16 Time-off-pick (seconds) of transgenic nematodes harboring tissue-specific aggregating protein species was assessed as previously described, 16,17 on three days (muscle polyQ, muscle Aβ 1-42 , TS∆ and respective controls) or four days (intestine polyQ, neuron polyQ, muscle α-synuclein and control) after having been plated on indicated bacteria as L1s.…”

Section: Motility Assaysmentioning

confidence: 99%

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Identification of proteotoxic and proteoprotective bacteria that non-specifically affect proteins associated with neurodegenerative diseases

Walker,

Bhargava,

Bucher

et al. 2023

Preprint

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Neurodegenerative protein conformational diseases (PCDs), such as Alzheimer's, Parkinson's, and Huntington's, are a leading cause of death and disability worldwide and have no known cures or effective treatments. Emerging evidence suggests a role for the gut microbiota in the pathogenesis of neurodegenerative PCDs; however, the influence of specific bacteria on the culprit proteins associated with each of these diseases remains elusive, primarily due to the complexity of the microbiota. In the present study, we employed a single-strain screening approach to identify human bacterial isolates that enhance or suppress the aggregation of culprit proteins and the associated toxicity in Caenorhabditis elegans expressing Abeta1-42, alpha-synuclein, and polyglutamine tracts. Here, we reveal the first comprehensive analysis of the human microbiome for its effect on proteins associated with neurodegenerative diseases. Our results suggest that bacteria affect the aggregation of metastable proteins by modulating host proteostasis rather than selectively targeting specific disease-associated proteins. These results reveal bacteria that potentially influence the pathogenesis of PCDs and open new promising prevention and treatment opportunities by altering the abundance of beneficial and detrimental microbes.

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Section: Resultsmentioning

confidence: 60%