Human trans-active response DNA binding protein 43 kDa (hTDP-43) is a protein necessary to the trafficking and processing of messenger ribonucleic acids (mRNA) in human cells but is also aggregation prone and has been implicated in amyotrophic lateral sclerosis (ALS). The structure of this multi-domain protein remains unknown, as each domain is linked by a disordered linker region. The C-terminal domain (CTD) is largely disordered, and the protein is 43 kDa and thus too large for many imaging techniques. hTDP-43 has been observed, both in vivo and in vitro, to form a native homodimer, but the precise interface of dimerization is unknown. The mechanism of aggregation is also unknown. As ALS is a disease currently without cure, anti-aggregation and dis-aggregase therapeutics are needed. This thesis sought to probe the structure of hTDP-43 with a battery of techniques to determine the structure of full-length hTDP-43 as well as to identify putative therapeutics to combat the aggregation of hTDP-43.
","abstract_html":"<p>Human trans-active response DNA binding protein 43 kDa (hTDP-43) is a protein necessary to the trafficking and processing of messenger ribonucleic acids (mRNA) in human cells but is also aggregation prone and has been implicated in amyotrophic lateral sclerosis (ALS). The structure of this multi-domain protein remains unknown, as each domain is linked by a disordered linker region. The C-terminal domain (CTD) is largely disordered, and the protein is 43 kDa and thus too large for many imaging techniques. hTDP-43 has been observed, both <em>in vivo</em> and <em>in vitro</em>, to form a native homodimer, but the precise interface of dimerization is unknown. The mechanism of aggregation is also unknown. As ALS is a disease currently without cure, anti-aggregation and dis-aggregase therapeutics are needed. This thesis sought to probe the structure of hTDP-43 with a battery of techniques to determine the structure of full-length hTDP-43 as well as to identify putative therapeutics to combat the aggregation of hTDP-43.</p>","abstract_has_math":false,"creators":["Oldani, Emily Grace"],"institution":null,"degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Sunil Kumar","Martin Margittai","Schuyler van Engelenberg","Scott Barbee"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-06-15T07:00:00Z","date_published":"2024-06-15T07:00:00Z","updated_at":"2026-07-24T02:01:48Z","subjects":["Structural biology","Aggregation prone proteins","Amyotrophic lateral sclerosis (ALS)","Protein-RNA interactions","Protein-protein interactions","TDP-43","Biochemistry","Biochemistry, Biophysics, and Structural Biology","Biophysics","Life Sciences","Molecular Biology"],"languages":["English (eng)"],"rights":["Copyright is held by the author. Permanently suppressed.
"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.du.edu/etd/2385","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Sunil Kumar","Martin Margittai","Schuyler van Engelenberg","Scott Barbee"]},{"key":"dc:creator","label":"Author","values":["Oldani, Emily Grace"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Structural biology","Aggregation prone proteins","Amyotrophic lateral sclerosis (ALS)","Protein-RNA interactions","Protein-protein interactions","TDP-43","Biochemistry","Biochemistry, Biophysics, and Structural Biology","Biophysics","Life Sciences","Molecular Biology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English (eng)"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright is held by the author. Permanently suppressed.
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"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Biophysical Characterization of the ALS-Linked Protein TDP-43; and Genetic and Small Molecule Rescues from Its Cytotoxicity"]}]}],"canonical_facts":{"dc:contributor":["Sunil Kumar","Martin Margittai","Schuyler van Engelenberg","Scott Barbee"],"dc:creator":["Oldani, Emily Grace"],"dc:description.abstract":["Human trans-active response DNA binding protein 43 kDa (hTDP-43) is a protein necessary to the trafficking and processing of messenger ribonucleic acids (mRNA) in human cells but is also aggregation prone and has been implicated in amyotrophic lateral sclerosis (ALS). The structure of this multi-domain protein remains unknown, as each domain is linked by a disordered linker region. The C-terminal domain (CTD) is largely disordered, and the protein is 43 kDa and thus too large for many imaging techniques. hTDP-43 has been observed, both in vivo and in vitro, to form a native homodimer, but the precise interface of dimerization is unknown. The mechanism of aggregation is also unknown. As ALS is a disease currently without cure, anti-aggregation and dis-aggregase therapeutics are needed. This thesis sought to probe the structure of hTDP-43 with a battery of techniques to determine the structure of full-length hTDP-43 as well as to identify putative therapeutics to combat the aggregation of hTDP-43.
"],"dc:format":["application/pdf"],"dc:identifier":["https://digitalcommons.du.edu/etd/2385"],"dc:language":["English (eng)"],"dc:rights":["Copyright is held by the author. Permanently suppressed.
"],"dc:subject":["Structural biology","Aggregation prone proteins","Amyotrophic lateral sclerosis (ALS)","Protein-RNA interactions","Protein-protein interactions","TDP-43","Biochemistry","Biochemistry, Biophysics, and Structural Biology","Biophysics","Life Sciences","Molecular Biology"],"dc:title":["Biophysical Characterization of the ALS-Linked Protein TDP-43; and Genetic and Small Molecule Rescues from Its Cytotoxicity"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."]},"updated_at":"2026-07-24T02:01:48Z"}