{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/108225"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/108225","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Serotonin transporter import","abstract":"Neurotransmitter Sodium Symporters modulate neurotransmission and members of this family of transporters are a popular target in the treatment of depression, addiction, obsessive compulsive disorder, and generalized anxiety disorder including the serotonin transporter and the dopamine transporter. These transporters have been the targets of numerous mutagenesis studies, none so expansive as our deep mutational scans, where we have characterized the effects of every point mutant on the function and surface localization of two of these proteins, the serotonin transporter (SERT) and the dopamine transporter (DAT). Collaborating with Diwakar Shukla’s group at UIUC, we have further advanced the understanding of function in these transporters by performing molecular dynamics simulations with and without various substrates. These simulations support our deep mutagenesis conclusions, while yielding novel information about the binding characteristics of both the native and non-native substrates for the human serotonin transporter, a representative member of this symporter family. Work with SERT and DAT lead us to hypothesize that the conformational equilibria of the transport cycle in these transporters is affected differentially for substrate import by mutations which stabilize sampling one conformation over another. Using molecular dynamics, we have observed a third ion binding site previously unrecognized in this transporter. Further, we have effectively used deep mutational scanning in yeast to engineer increased receptor-ligand affinity utilizing the PDGF-B PDGFRß system.","abstract_html":"Neurotransmitter Sodium Symporters modulate neurotransmission and members of this family of transporters are a popular target in the treatment of depression, addiction, obsessive compulsive disorder, and generalized anxiety disorder including the serotonin transporter and the dopamine transporter. These transporters have been the targets of numerous mutagenesis studies, none so expansive as our deep mutational scans, where we have characterized the effects of every point mutant on the function and surface localization of two of these proteins, the serotonin transporter (SERT) and the dopamine transporter (DAT). Collaborating with Diwakar Shukla’s group at UIUC, we have further advanced the understanding of function in these transporters by performing molecular dynamics simulations with and without various substrates. These simulations support our deep mutagenesis conclusions, while yielding novel information about the binding characteristics of both the native and non-native substrates for the human serotonin transporter, a representative member of this symporter family. Work with SERT and DAT lead us to hypothesize that the conformational equilibria of the transport cycle in these transporters is affected differentially for substrate import by mutations which stabilize sampling one conformation over another. Using molecular dynamics, we have observed a third ion binding site previously unrecognized in this transporter. Further, we have effectively used deep mutational scanning in yeast to engineer increased receptor-ligand affinity utilizing the PDGF-B PDGFRß system.","abstract_has_math":false,"creators":["Young, Heather J"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Biochemistry","degree_department":null,"school":null,"contributors":["Procko, Erik","Gennis, Robert","Jin, Hong","Pogorelov, Taras"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2020,"date_issued":"2020-08-27T00:46:51Z","date_published":"2020-08-27T00:46:51Z","updated_at":"2026-07-22T22:24:48Z","subjects":["Serotonin","Transporter","Neurotransmitter Transporter","PDGF","SERT","Dopamine","Dopamine Transporter","DAT"],"languages":["en"],"rights":["Copyright 2020 Heather J Young"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/108225","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Procko, Erik","Gennis, Robert","Jin, Hong","Pogorelov, Taras"]},{"key":"dc:creator","label":"Author","values":["Young, Heather J"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2020-08-27T00:46:51Z","2022-08-27T00:51:40Z","2020-02-27","2020-05"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Serotonin","Transporter","Neurotransmitter Transporter","PDGF","SERT","Dopamine","Dopamine Transporter","DAT"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2020 Heather J Young"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/108225"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Neurotransmitter Sodium Symporters modulate neurotransmission and members of this family of transporters are a popular target in the treatment of depression, addiction, obsessive compulsive disorder, and generalized anxiety disorder including the serotonin transporter and the dopamine transporter. These transporters have been the targets of numerous mutagenesis studies, none so expansive as our deep mutational scans, where we have characterized the effects of every point mutant on the function and surface localization of two of these proteins, the serotonin transporter (SERT) and the dopamine transporter (DAT). Collaborating with Diwakar Shukla’s group at UIUC, we have further advanced the understanding of function in these transporters by performing molecular dynamics simulations with and without various substrates. These simulations support our deep mutagenesis conclusions, while yielding novel information about the binding characteristics of both the native and non-native substrates for the human serotonin transporter, a representative member of this symporter family. Work with SERT and DAT lead us to hypothesize that the conformational equilibria of the transport cycle in these transporters is affected differentially for substrate import by mutations which stabilize sampling one conformation over another. Using molecular dynamics, we have observed a third ion binding site previously unrecognized in this transporter. Further, we have effectively used deep mutational scanning in yeast to engineer increased receptor-ligand affinity utilizing the PDGF-B PDGFRß system.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2022-05-01","The student, Heather Young, accepted the attached license on 2020-02-25 at 11:34.","The student, Heather Young, submitted this Dissertation for approval on 2020-02-25 at 11:42.","This Dissertation was approved for publication on 2020-02-27 at 16:22.","DSpace SAF Submission Ingestion Package generated from Vireo submission #14878 on 2020-08-25 at 17:38:49","Made available in DSpace on 2020-08-27T00:46:51Z (GMT). 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These transporters have been the targets of numerous mutagenesis studies, none so expansive as our deep mutational scans, where we have characterized the effects of every point mutant on the function and surface localization of two of these proteins, the serotonin transporter (SERT) and the dopamine transporter (DAT). Collaborating with Diwakar Shukla’s group at UIUC, we have further advanced the understanding of function in these transporters by performing molecular dynamics simulations with and without various substrates. These simulations support our deep mutagenesis conclusions, while yielding novel information about the binding characteristics of both the native and non-native substrates for the human serotonin transporter, a representative member of this symporter family. Work with SERT and DAT lead us to hypothesize that the conformational equilibria of the transport cycle in these transporters is affected differentially for substrate import by mutations which stabilize sampling one conformation over another. Using molecular dynamics, we have observed a third ion binding site previously unrecognized in this transporter. Further, we have effectively used deep mutational scanning in yeast to engineer increased receptor-ligand affinity utilizing the PDGF-B PDGFRß system.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2022-05-01","The student, Heather Young, accepted the attached license on 2020-02-25 at 11:34.","The student, Heather Young, submitted this Dissertation for approval on 2020-02-25 at 11:42.","This Dissertation was approved for publication on 2020-02-27 at 16:22.","DSpace SAF Submission Ingestion Package generated from Vireo submission #14878 on 2020-08-25 at 17:38:49","Made available in DSpace on 2020-08-27T00:46:51Z (GMT). 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