{"id":{"repo_id":"uoit","oai_identifier":"oai:ontariotechu.scholaris.ca:10155/1729"},"canonical_url":"https://search.dev.ndltd.org/etd/uoit/oai:ontariotechu.scholaris.ca:10155/1729","repository":{"repo_id":"uoit","name":"Ontario Institute of Technology","base_url":"https://ontariotechu.scholaris.ca/server/oai/request"},"display":{"title":"The identification of novel cys-loop receptor genes in Dirofilaria immitis","abstract":"Dirofilaria immitis is a parasitic nematode responsible for canine heartworm disease. Currently, heartworm treatments rely primarily on a single drug class – the macrocyclic lactones – but anthelmintic resistance is emerging. Cys-loop ligand-gated ion channels are an untapped source for drug targets essential for nematode neurotransmission. This thesis presents the isolation and preliminary pharmacological characterization of three inhibitory D. immitis ion channels: GLC-2, GLC-4, and LGC-49. These genes are conserved across nematode species and expressed throughout the D. immitis life-cycle, as demonstrated by phylogenetic analysis and RT-qPCR. Dim-GLC-2 forms a monosodium L-glutamate (MSG) and L-glutamic acid sensitive homomeric channel, whereas the Dim-GLC-2/Dim-GLC-4 heteromeric channel shows reduced MSG current amplitude. The Dim-LGC-49 homomeric channel is responsive to cholinergic compounds. Homology modelling of homomeric channels highlights binding pocket residues which may interact with ligands. This research provides additional information on cys-loop receptors in parasitic nematodes crucial for understanding the action of potential new drugs.","abstract_html":"Dirofilaria immitis is a parasitic nematode responsible for canine heartworm disease. Currently, heartworm treatments rely primarily on a single drug class – the macrocyclic lactones – but anthelmintic resistance is emerging. Cys-loop ligand-gated ion channels are an untapped source for drug targets essential for nematode neurotransmission. This thesis presents the isolation and preliminary pharmacological characterization of three inhibitory D. immitis ion channels: GLC-2, GLC-4, and LGC-49. These genes are conserved across nematode species and expressed throughout the D. immitis life-cycle, as demonstrated by phylogenetic analysis and RT-qPCR. Dim-GLC-2 forms a monosodium L-glutamate (MSG) and L-glutamic acid sensitive homomeric channel, whereas the Dim-GLC-2/Dim-GLC-4 heteromeric channel shows reduced MSG current amplitude. The Dim-LGC-49 homomeric channel is responsive to cholinergic compounds. Homology modelling of homomeric channels highlights binding pocket residues which may interact with ligands. This research provides additional information on cys-loop receptors in parasitic nematodes crucial for understanding the action of potential new drugs.","abstract_has_math":false,"creators":["Nichols, Jennifer S."],"institution":"University of Ontario Institute of Technology","degree_name":"Master of Science (MSc)","degree_level":null,"degree_discipline":"Applied Bioscience","degree_department":null,"school":null,"contributors":[],"advisors":["Forrester, Sean"],"committee_chairs":[],"committee_members":[],"year":2023,"date_issued":"2023-10-01","date_published":"2023-10-01","updated_at":"2026-07-24T05:35:24Z","subjects":["Heartworm","Cys-loop LGICs","Dirofilaria immitis","Anthelmintic resistance"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/10155/1729","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Forrester, Sean"]},{"key":"dc:creator","label":"Author","values":["Nichols, Jennifer S."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-01-23T21:15:18Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2024-01-23T21:15:18Z"]},{"key":"dc:date.issued","label":"Date","values":["2023-10-01"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Applied Bioscience"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science (MSc)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Ontario Institute of Technology"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Heartworm","Cys-loop LGICs","Dirofilaria immitis","Anthelmintic resistance"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10155/1729"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Dirofilaria immitis is a parasitic nematode responsible for canine heartworm disease. Currently, heartworm treatments rely primarily on a single drug class – the macrocyclic lactones – but anthelmintic resistance is emerging. Cys-loop ligand-gated ion channels are an untapped source for drug targets essential for nematode neurotransmission. This thesis presents the isolation and preliminary pharmacological characterization of three inhibitory D. immitis ion channels: GLC-2, GLC-4, and LGC-49. These genes are conserved across nematode species and expressed throughout the D. immitis life-cycle, as demonstrated by phylogenetic analysis and RT-qPCR. Dim-GLC-2 forms a monosodium L-glutamate (MSG) and L-glutamic acid sensitive homomeric channel, whereas the Dim-GLC-2/Dim-GLC-4 heteromeric channel shows reduced MSG current amplitude. The Dim-LGC-49 homomeric channel is responsive to cholinergic compounds. Homology modelling of homomeric channels highlights binding pocket residues which may interact with ligands. This research provides additional information on cys-loop receptors in parasitic nematodes crucial for understanding the action of potential new drugs."]},{"key":"dc:title","label":"Title","values":["The identification of novel cys-loop receptor genes in Dirofilaria immitis"]}]}],"canonical_facts":{"dc:contributor.advisor":["Forrester, Sean"],"dc:creator":["Nichols, Jennifer S."],"dc:date.accessioned":["2024-01-23T21:15:18Z"],"dc:date.available":["2024-01-23T21:15:18Z"],"dc:date.issued":["2023-10-01"],"dc:description.abstract":["Dirofilaria immitis is a parasitic nematode responsible for canine heartworm disease. Currently, heartworm treatments rely primarily on a single drug class – the macrocyclic lactones – but anthelmintic resistance is emerging. Cys-loop ligand-gated ion channels are an untapped source for drug targets essential for nematode neurotransmission. This thesis presents the isolation and preliminary pharmacological characterization of three inhibitory D. immitis ion channels: GLC-2, GLC-4, and LGC-49. These genes are conserved across nematode species and expressed throughout the D. immitis life-cycle, as demonstrated by phylogenetic analysis and RT-qPCR. Dim-GLC-2 forms a monosodium L-glutamate (MSG) and L-glutamic acid sensitive homomeric channel, whereas the Dim-GLC-2/Dim-GLC-4 heteromeric channel shows reduced MSG current amplitude. The Dim-LGC-49 homomeric channel is responsive to cholinergic compounds. Homology modelling of homomeric channels highlights binding pocket residues which may interact with ligands. This research provides additional information on cys-loop receptors in parasitic nematodes crucial for understanding the action of potential new drugs."],"dc:identifier.uri":["https://hdl.handle.net/10155/1729"],"dc:language.iso":["en"],"dc:subject":["Heartworm","Cys-loop LGICs","Dirofilaria immitis","Anthelmintic resistance"],"dc:title":["The identification of novel cys-loop receptor genes in Dirofilaria immitis"],"dc:type":["Thesis"],"thesis:degree_discipline":["Applied Bioscience"],"thesis:degree_name":["Master of Science (MSc)"],"thesis:institution_name":["University of Ontario Institute of Technology"]},"updated_at":"2026-07-24T05:35:24Z"}