{"675501":{"#nid":"675501","#data":{"type":"event","title":"BioE PhD Defense Presentation-  Nikki McArthur ","body":[{"value":"\u003Cp\u003E\u003Cstrong\u003EAdvisor:\u003C\/strong\u003E\u0026nbsp;Ravi Kane, Ph.D. (Chemical and Biomolecular Engineering)\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECommittee Members:\u003C\/strong\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EJohn Blazeck, Ph.D. (Chemical and Biomolecular Engineering)\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EJulie Champion, Ph.D. (Chemical and Biomolecular Engineering)\u0026nbsp;\u003C\/p\u003E\u003Cp\u003ECorey Wilson, Ph.D. (Chemical and Biomolecular Engineering)\u0026nbsp;\u003C\/p\u003E\u003Cp\u003ELevi Wood, Ph.D. (Mechanical Engineering)\u0026nbsp;\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EEngineering Multivalent Nanobodies Against Amyloid Proteins and Other Antigens\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u2002\u2002\u2002\u2002\u2002\u2002Tauopathies, such as Alzheimer\u2019s disease, are neurodegenerative diseases that involve the misfolding and deposition of aggregates of the amyloid protein tau. These diseases are among the most widespread neurodegenerative diseases, yet there are few safe and effective disease-modifying treatments for them. Conformational antibodies and antibody fragments that target the various aggregate forms of tau are promising candidates for treatments to slow the progression of these tauopathies and are useful as reagents to understand the aggregation of tau and its role in disease progression. In this dissertation, we have explored the \u003Cem\u003Ein vitro\u003C\/em\u003E\u0026nbsp;development and characterization of multivalent nanobodies, or single-domain antibody fragments, targeting complex and heterogeneous tau aggregates.\u003C\/p\u003E\u003Cp\u003E\u2002\u2002\u2002\u2002\u2002\u2002We began with the development of a simple approach using a synthetic yeast surface display nanobody library and \u003Cem\u003Ein vitro\u003C\/em\u003E\u0026nbsp;cell sorting to identify a pan-tau nanobody with specificity for tau protein relative to other amyloid proteins. We have shown that multivalent versions of our lead tau-binding nanobody have increased avidity towards tau aggregates and recognize pathogenic tau found in the brains of tau transgenic mice. We have also characterized tau fibril-specific nanobodies and modified them for improved delivery past the blood-brain barrier. Next, we modified our sorting strategy to generate conformational nanobodies that target oligomeric tau, a form of aggregated tau which is suspected to be the most toxic form present in Alzheimer\u2019s disease. We demonstrated that our nanobodies are specific for tau oligomers relative to tau monomer and fibrils and bind to tau oligomers in brain samples from Alzheimer\u2019s disease patients. We have extended this work to screen for nanobodies that target oligomers of another amyloid protein involved in Alzheimer\u2019s disease, amyloid-\u03b2. Finally, we applied our \u003Cem\u003Ein vitro\u003C\/em\u003E\u0026nbsp;antibody discovery strategies to target an antigen involved in infectious disease\u2014the spike protein of the SARS-CoV-2 virus. We created multivalent nanobodies that bind with high affinity to the XBB spike protein and provide protection against an XBB challenge in mice.\u003C\/p\u003E\u003Cp\u003E\u2002\u2002\u2002\u2002\u2002\u2002Overall, this work demonstrates significant progress in the development and characterization of nanobodies specific for complex multimeric antigens. The multivalent nanobodies that we have generated can be used to study amyloid proteins and their involvement in neurodegenerative disease progression and can be further engineered into potent therapies for neurodegenerative or infectious diseases.\u003C\/p\u003E\u003Cp\u003E\u003Ca href=\u0022https:\/\/gatech.zoom.us\/j\/98028112546?pwd=Z8sNubJKxIZUoaJnJgAaJvsCHex2wo.1\u0022\u003Ehttps:\/\/gatech.zoom.us\/j\/98028112546?pwd=Z8sNubJKxIZUoaJnJgAaJvsCHex2wo.1\u003C\/a\u003E\u003C\/p\u003E","summary":"","format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EBioE PhD Defense Presentation- \u0026nbsp;\u0022Engineering Multivalent Nanobodies Against Amyloid Proteins and Other Antigens\u0022- Nikki McArthur\u0026nbsp;\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"\u0022Engineering Multivalent Nanobodies Against Amyloid Proteins and Other Antigens\u0022"}],"uid":"27917","created_gmt":"2024-07-17 14:56:41","changed_gmt":"2024-07-17 14:56:41","author":"Laura Paige","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2024-07-24T13:30:00-04:00","event_time_end":"2024-07-24T15:30:00-04:00","event_time_end_last":"2024-07-24T15:30:00-04:00","gmt_time_start":"2024-07-24 17:30:00","gmt_time_end":"2024-07-24 19:30:00","gmt_time_end_last":"2024-07-24 19:30:00","rrule":null,"timezone":"America\/New_York"},"location":"1128 IBB","extras":[],"groups":[{"id":"65448","name":"Bioengineering Graduate Program"}],"categories":[],"keywords":[{"id":"172056","name":"go-BioE"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[],"email":[],"slides":[],"orientation":[],"userdata":""}}}