{"id":{"repo_id":"uoit","oai_identifier":"oai:ontariotechu.scholaris.ca:10155/483"},"canonical_url":"https://search.dev.ndltd.org/etd/uoit/oai:ontariotechu.scholaris.ca:10155/483","repository":{"repo_id":"uoit","name":"Ontario Institute of Technology","base_url":"https://ontariotechu.scholaris.ca/server/oai/request"},"display":{"title":"Investigation into the role of binding loop E on the function of the nematode cys-loop GABA receptor.","abstract":"Haemonchus contortus is a parasitic nematode that infects the abomasum of ruminants. While several classes of anthelmintic drugs exist to control nematode infections, H. contortus is resistant to all of them. Therefore, novel drug targets such as ligand-gated chloride channels (LGCCs) need to be characterized. The objective of this thesis was to further characterize the agonist binding pocket in Hco-UNC-49BC, the LGCC gated by γ- aminobutyric acid (GABA) within H. contortus. To meet this objective, each amino acid residue in binding loop E was changed to a cysteine and analyzed via electrophysiology and the substituted cysteine accessibility method. It was found that of the 18 loop E mutants analyzed, His142, Ser144, Arg147, and Ser157, all played a role in channel activation and were sensitive to modification by a methanethiosulfonate reagent. In addition, mutants lacking His142 showed increased sensitivity to a variety of agonists and produced maximal chloride conductance to the previously characterized partial agonist 5-aminovaleric acid. Overall, this thesis has revealed potential differences in the agonist binding pocket between nematode UNC-49 and mammalian GABA receptors that could be exploited in the design of novel anthelmintics.","abstract_html":"Haemonchus contortus is a parasitic nematode that infects the abomasum of ruminants. While several classes of anthelmintic drugs exist to control nematode infections, H. contortus is resistant to all of them. Therefore, novel drug targets such as ligand-gated chloride channels (LGCCs) need to be characterized. The objective of this thesis was to further characterize the agonist binding pocket in Hco-UNC-49BC, the LGCC gated by γ- aminobutyric acid (GABA) within H. contortus. To meet this objective, each amino acid residue in binding loop E was changed to a cysteine and analyzed via electrophysiology and the substituted cysteine accessibility method. It was found that of the 18 loop E mutants analyzed, His142, Ser144, Arg147, and Ser157, all played a role in channel activation and were sensitive to modification by a methanethiosulfonate reagent. In addition, mutants lacking His142 showed increased sensitivity to a variety of agonists and produced maximal chloride conductance to the previously characterized partial agonist 5-aminovaleric acid. Overall, this thesis has revealed potential differences in the agonist binding pocket between nematode UNC-49 and mammalian GABA receptors that could be exploited in the design of novel anthelmintics.","abstract_has_math":false,"creators":["Kwaka, Ariel Deborah"],"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":2014,"date_issued":"2014-12-01","date_published":"2014-12-01","updated_at":"2026-07-24T05:35:39Z","subjects":["Haemonchus contortus","Hco-UNC-49","GABA","Loop-E","Substituted cysteine accessibility method","Ligand-gated chloride channel"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/10155/483","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":["Kwaka, Ariel Deborah"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2014-12-22T21:56:32Z","2022-03-30T17:04:46Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2014-12-22T21:56:32Z","2022-03-30T17:04:46Z"]},{"key":"dc:date.issued","label":"Date","values":["2014-12-01"]},{"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":["Haemonchus contortus","Hco-UNC-49","GABA","Loop-E","Substituted cysteine accessibility method","Ligand-gated chloride channel"]}]},{"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/10155/483"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Haemonchus contortus is a parasitic nematode that infects the abomasum of ruminants. While several classes of anthelmintic drugs exist to control nematode infections, H. contortus is resistant to all of them. Therefore, novel drug targets such as ligand-gated chloride channels (LGCCs) need to be characterized. The objective of this thesis was to further characterize the agonist binding pocket in Hco-UNC-49BC, the LGCC gated by γ- aminobutyric acid (GABA) within H. contortus. To meet this objective, each amino acid residue in binding loop E was changed to a cysteine and analyzed via electrophysiology and the substituted cysteine accessibility method. It was found that of the 18 loop E mutants analyzed, His142, Ser144, Arg147, and Ser157, all played a role in channel activation and were sensitive to modification by a methanethiosulfonate reagent. In addition, mutants lacking His142 showed increased sensitivity to a variety of agonists and produced maximal chloride conductance to the previously characterized partial agonist 5-aminovaleric acid. Overall, this thesis has revealed potential differences in the agonist binding pocket between nematode UNC-49 and mammalian GABA receptors that could be exploited in the design of novel anthelmintics."]},{"key":"dc:title","label":"Title","values":["Investigation into the role of binding loop E on the function of the nematode cys-loop GABA receptor."]}]}],"canonical_facts":{"dc:contributor.advisor":["Forrester, Sean"],"dc:creator":["Kwaka, Ariel Deborah"],"dc:date.accessioned":["2014-12-22T21:56:32Z","2022-03-30T17:04:46Z"],"dc:date.available":["2014-12-22T21:56:32Z","2022-03-30T17:04:46Z"],"dc:date.issued":["2014-12-01"],"dc:description.abstract":["Haemonchus contortus is a parasitic nematode that infects the abomasum of ruminants. While several classes of anthelmintic drugs exist to control nematode infections, H. contortus is resistant to all of them. Therefore, novel drug targets such as ligand-gated chloride channels (LGCCs) need to be characterized. The objective of this thesis was to further characterize the agonist binding pocket in Hco-UNC-49BC, the LGCC gated by γ- aminobutyric acid (GABA) within H. contortus. To meet this objective, each amino acid residue in binding loop E was changed to a cysteine and analyzed via electrophysiology and the substituted cysteine accessibility method. It was found that of the 18 loop E mutants analyzed, His142, Ser144, Arg147, and Ser157, all played a role in channel activation and were sensitive to modification by a methanethiosulfonate reagent. In addition, mutants lacking His142 showed increased sensitivity to a variety of agonists and produced maximal chloride conductance to the previously characterized partial agonist 5-aminovaleric acid. Overall, this thesis has revealed potential differences in the agonist binding pocket between nematode UNC-49 and mammalian GABA receptors that could be exploited in the design of novel anthelmintics."],"dc:identifier.uri":["https://hdl.handle.net/10155/483"],"dc:language.iso":["en"],"dc:subject":["Haemonchus contortus","Hco-UNC-49","GABA","Loop-E","Substituted cysteine accessibility method","Ligand-gated chloride channel"],"dc:title":["Investigation into the role of binding loop E on the function of the nematode cys-loop GABA receptor."],"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":"2026-07-24T05:35:39Z"}