{"673532":{"#nid":"673532","#data":{"type":"event","title":"PhD Defense by Luke Knudson","body":[{"value":"\u003Cp\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003ELuke Knudson\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003Cbr \/\u003E\r\n\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003EBME PhD Defense Presentation\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003Cbr \/\u003E\r\n\u003Cbr \/\u003E\r\n\u003Cstrong\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003EDate\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/strong\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E: 2024-03-26\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003Cbr \/\u003E\r\n\u003Cstrong\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003ETime\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/strong\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E: 9:00 AM\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003Cbr \/\u003E\r\n\u003Cstrong\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003ELocation \/ Meeting Link\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/strong\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E: Whitehead Biomedical Research Building, Room 400 \/ \u003Ca href=\u0022https:\/\/zoom.us\/j\/98305218144?pwd=M0JuaFdPKzc0V1ZPWmpBYTBsS1NJUT09\u0026amp;from=addon\u0022\u003Ehttps:\/\/zoom.us\/j\/98305218144?pwd=M0JuaFdPKzc0V1ZPWmpBYTBsS1NJUT09\u0026amp;from=addon\u003C\/a\u003E Meeting ID: 983 0521 8144 (Passcode: 415)\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003Cbr \/\u003E\r\n\u003Cbr \/\u003E\r\n\u003Cstrong\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003ECommittee Members:\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/strong\u003E\u003Cbr \/\u003E\r\n\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003EDr. Gary J. Bassell (Advisor); Dr. Philip Santangelo; Dr. Karmella Haynes; Dr. Anita Corbett; Dr. Dorothy Lerit\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003Cbr \/\u003E\r\n\u003Cbr \/\u003E\r\n\u003Cbr \/\u003E\r\n\u003Cstrong\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003ETitle\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/strong\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E: Muscleblind Protein-Protein Interactions: Implications for RNA Biology and Myotonic Dystrophy Type 1 Pathogenesis\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003Cbr \/\u003E\r\n\u003Cbr \/\u003E\r\n\u003Cstrong\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003EAbstract:\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/strong\u003E\u003Cbr \/\u003E\r\n\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003ERNA granules are membrane-less condensates composed of various RNA-protein complexes, which are essential for post-transcriptional regulation of gene expression. However, RNA granules also have the potential to form the basis of disease pathogenesis, such as in Myotonic Dystrophy Type 1 (DM1). DM1 is a monogenic disorder in which CTG repeats in the gene DMPK are expanded. When transcribed, these CUG repeats form toxic RNA foci that sequester the Muscleblind-like (MBNL) family of RNA binding proteins (RBPs) in the nucleus. In a non-disease setting, MBNLs normally regulate alternative splicing (AS) and localize mRNA, though the mechanisms underlying the later had remained unclear. Using imaging and biochemical approaches, we demonstrated that kinesin motor proteins KIF1B\u03b1 and KIF1C selectively interact with and transport MBNL1 granules. This finding and the lack of a comprehensive MBNL interactome motivated us to conduct proteomics on immunoprecipitated MBNL1. In addition to numerous novel interactors, we noted that MBNL interacts with itself. The exact forces that hold RNA granules together are not well understood despite their importance in RNA granule dynamics. We hypothesized that disulfide bonds are involved in MBNL dimerization, a process that influences MBNL1\u2019s regulation of AS and DM1 pathogenesis. Here we identify the precise cysteine residues responsible for MBNL dimerization. We also use cysteine mutants and RNA sequencing to highlight the importance of MBNL1 dimerization in its regulation of AS. Finally, we demonstrate that MBNL1 dimerization is needed to maintain DM1 foci integrity. These results provide insight into the pathological mechanisms of DM1 and suggest other RBPs might dimerize similarly to regulate function.\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/p\u003E\r\n","summary":"","format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003E\u003Cspan\u003EMuscleblind Protein-Protein Interactions: Implications for RNA Biology and Myotonic Dystrophy Type 1 Pathogenesis\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/span\u003E\u003C\/p\u003E\r\n","format":"limited_html"}],"field_summary_sentence":[{"value":"Muscleblind Protein-Protein Interactions: Implications for RNA Biology and Myotonic Dystrophy Type 1 Pathogenesis"}],"uid":"27707","created_gmt":"2024-03-14 16:21:39","changed_gmt":"2024-03-14 16:21:38","author":"Tatianna Richardson","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2024-03-26T09:00:00-04:00","event_time_end":"2024-03-26T11:00:00-04:00","event_time_end_last":"2024-03-26T11:00:00-04:00","gmt_time_start":"2024-03-26 13:00:00","gmt_time_end":"2024-03-26 15:00:00","gmt_time_end_last":"2024-03-26 15:00:00","rrule":null,"timezone":"America\/New_York"},"location":"Whitehead Biomedical Research Building, Room 400 \/ ","extras":[],"groups":[{"id":"221981","name":"Graduate Studies"}],"categories":[],"keywords":[{"id":"100811","name":"Phd Defense"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1788","name":"Other\/Miscellaneous"}],"invited_audience":[{"id":"78771","name":"Public"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[],"email":[],"slides":[],"orientation":[],"userdata":""}}}