{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/78581"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/78581","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Molecular Mechanisms Underlying Suppression of Neurodegeneration in the Drosophila model of Leigh Syndrome","abstract":"M.S.","abstract_html":"M.S.","abstract_has_math":false,"creators":["Bhatnagar, Akanksha"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Singh, Satpal","Pharmacology and Toxicology"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-10-26T02:55:55Z","date_published":"2018-10-26T02:55:55Z","updated_at":"2026-07-27T19:05:12Z","subjects":["pharmacology"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/78581","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Singh, Satpal","Pharmacology and Toxicology"]},{"key":"dc:creator","label":"Author","values":["Bhatnagar, Akanksha"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2018-10-26T02:55:55Z","2018","2018-08-08 23:21:33"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["pharmacology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/78581"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["M.S.","Background: Leigh Syndrome (LS) is an early-onset neurodegenerative disorder (ND) characterized by progressive loss of mental and movement abilities. Presently, the disease has no cure and usually leads to lethality. The Drosophila model of LS, levy, shows temperature-sensitive (TS) paralysis, reduced life span, and progressive neurodegeneration in flies. A second mutation, Suppressor of levy (Su(levy)), moderately rescues these neurodegenerative phenotypes. Preliminary data suggests that the microRNA processor, drosha, underlies the Su(levy) mutation.Aim: Identify the Su(levy) gene and characterize the molecular pathways associated with the Su(levy) mediated suppression of neurodegeneration.Methods: Three separate loss-of-function drosha alleles were tested for phenotypic similarities with Su(levy) using complementation tests and TS paralysis assays. Homozygous lethality stage in Su(levy) and drosha alleles was determined. Sanger sequencing was performed on the drosha gene of the Su(levy) strain. Alleles of other non-coding RNA processing genes were analyzed for the Su(levy) mediated suppressive phenotype.Results: Su(levy) plays a general protective role and delays TS paralysis in wild type and levy mutants. Similar to Su(levy), each drosha allele tested delayed TS paralysis in CS and levy flies. Further, Su(levy) failed to complement two drosha alleles, suggesting the two mutations could be present in the same gene. Sanger sequencing revealed four potential mutations in the drosha gene region in the Su(levy) strain. Unlike drosha and Su(levy) mutants, canonical microRNA, mirtron and siRNA processing associated alleles failed to delay TS paralysis in wild type and levy mutants.Conclusion: Data suggests that Su(levy) is a mutation in the drosha gene. Significance: The results from this project will provide a lead for therapeutic intervention of LS as well as indicate the likely mechanisms altered by the disease itself. In the future, pharmacological studies can then be utilized to design a drug that mimics the role of Su(levy), which can be used as a therapy in humans."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Molecular Mechanisms Underlying Suppression of Neurodegeneration in the Drosophila model of Leigh Syndrome"]}]}],"canonical_facts":{"dc:contributor":["Singh, Satpal","Pharmacology and Toxicology"],"dc:creator":["Bhatnagar, Akanksha"],"dc:date":["2018-10-26T02:55:55Z","2018","2018-08-08 23:21:33"],"dc:description":["M.S.","Background: Leigh Syndrome (LS) is an early-onset neurodegenerative disorder (ND) characterized by progressive loss of mental and movement abilities. Presently, the disease has no cure and usually leads to lethality. The Drosophila model of LS, levy, shows temperature-sensitive (TS) paralysis, reduced life span, and progressive neurodegeneration in flies. A second mutation, Suppressor of levy (Su(levy)), moderately rescues these neurodegenerative phenotypes. Preliminary data suggests that the microRNA processor, drosha, underlies the Su(levy) mutation.Aim: Identify the Su(levy) gene and characterize the molecular pathways associated with the Su(levy) mediated suppression of neurodegeneration.Methods: Three separate loss-of-function drosha alleles were tested for phenotypic similarities with Su(levy) using complementation tests and TS paralysis assays. Homozygous lethality stage in Su(levy) and drosha alleles was determined. Sanger sequencing was performed on the drosha gene of the Su(levy) strain. Alleles of other non-coding RNA processing genes were analyzed for the Su(levy) mediated suppressive phenotype.Results: Su(levy) plays a general protective role and delays TS paralysis in wild type and levy mutants. Similar to Su(levy), each drosha allele tested delayed TS paralysis in CS and levy flies. Further, Su(levy) failed to complement two drosha alleles, suggesting the two mutations could be present in the same gene. Sanger sequencing revealed four potential mutations in the drosha gene region in the Su(levy) strain. Unlike drosha and Su(levy) mutants, canonical microRNA, mirtron and siRNA processing associated alleles failed to delay TS paralysis in wild type and levy mutants.Conclusion: Data suggests that Su(levy) is a mutation in the drosha gene. Significance: The results from this project will provide a lead for therapeutic intervention of LS as well as indicate the likely mechanisms altered by the disease itself. In the future, pharmacological studies can then be utilized to design a drug that mimics the role of Su(levy), which can be used as a therapy in humans."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/78581"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["pharmacology"],"dc:title":["Molecular Mechanisms Underlying Suppression of Neurodegeneration in the Drosophila model of Leigh Syndrome"],"dc:type":["Text","Thesis"]},"updated_at":"2026-07-27T19:05:12Z"}