In-vitro analysis of microfilariae phenotypic responses induced by small molecules and dsRNA targeting receptor pathways

Filarial nematodes such as Brugia malayi and Dirofilaria immitis pose a significant threat to humans and companion animals. Current methods of control include a range of anthelmintics. However, with resistance on the rise, drug target discovery and development are urgently needed. This study explores phenotypic responses in microfilariae to small molecules as well as dsRNA molecules targeting genes involved in receptor pathways essential for nematode function. Utilizing the video analysis software called the Worminator, we quantified changes in movement upon exposure to agonists and antagonists acting on various receptors. Distinct responses were observed based on receptor modulation and small-molecule combinations, revealing potential synergies and antagonisms. Additionally, dsRNA targeting GluCl, nACh, and GABA receptor subunit genes resulted in significant gene silencing and corresponding phenotypic changes in nematode movement. These findings contribute to understanding parasitic nematode neurobiology and highlight receptor pathways as targets for novel anthelmintics.

Name thesis:degree_name

Master of Science (MSc)

Discipline thesis:degree_discipline

Applied Bioscience

Grantor

University of Ontario Institute of Technology

Year dc:date.issued

2024

Author dc:creator

• Petch, Amy

Advisor dc:contributor.advisor

• Forrester, Sean

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/10155/1902

OAI identifier oai:identifier

oai:ontariotechu.scholaris.ca:10155/1902