{ "142316-21890509": { "datetime_modified":"20251202T115857", "datetime_start":"20251211T150000", "datetime_end":"20251211T160000", "has_end_time":1, "date_start":"2025-12-11", "date_end":"2025-12-11", "time_start":"15:00:00", "time_end":"16:00:00", "time_zone":"America\/Detroit", "event_title":"Dissertation Defense Seminar: Cassandra Zuckerman", "occurrence_title":"", "combined_title":"Dissertation Defense Seminar: Cassandra Zuckerman: Investigation of shelterin complex assembly at C. elegans telomeres and structural characterization of a novel centrosomal protein complex critical for mammalian sperm development", "event_subtitle":"Investigation of shelterin complex assembly at C. elegans telomeres and structural characterization of a novel centrosomal protein complex critical for mammalian sperm development", "event_type":"Workshop \/ Seminar", "event_type_id":"21", "description":"Telomeres are nucleoprotein complexes at chromosome termini that are vital for the preservation of genome integrity. Telomeric DNA consists of hexad repeats (GGTTAG in mammals) that are mostly double-stranded (ds), ending in a short, single-stranded (ss) 3\u2032 overhang. In dividing cells, telomeric DNA shortens with each round of DNA replication, causing the \u201cend replication problem.\u201d A specialized ribonucleoprotein (RNP) enzyme, telomerase, replenishes telomeric DNA repeats to aid in resolving this problem. \r\nNatural chromosome ends resemble dsDNA breaks, creating the \u201cend protection problem,\u201d the necessity to protect natural ends from the DNA damage response\/repair machinery. The six-protein mammalian shelterin complex binds telomeric repeats to protect chromosome ends from unwanted repair. Shelterin dysfunction results in end deprotection and mouse embryonic lethality. POT1 is a critical shelterin component that protects the telomeric ssDNA overhang and the ds\u2013ss junction, and helps facilitate telomerase action. Thus, a single POT1 orchestrates multiple telomeric functions, complicating the dissection of its functions individually. Studying the shelterin complex in in toto is even more challenging, as POT1 is separated from the dsDNA-binding shelterin proteins by two additional shelterin subunits. \r\n\r\nIn contrast to humans, C. elegans (Ce) has four putative POT1 homologs (Ce POT-1, POT-2, POT-3, and MRT-1), leading us to hypothesize that POT1 functions are separated on different polypeptides, making it feasible to study each POT1 function individually. The dsDNA-binding proteins of C. elegans have also been discovered, and they bind directly to CePOT-1, greatly simplifying the composition of the shelterin complex. However, how the other CePOT1 homologs integrate into shelterin to protect and replicate chromosome ends is not known. Through my doctoral studies, I discovered a novel interaction of CePOT-1 with CePOT-2 and Ce-MRT-1 via a CePOT-1 binding site shared by CePOT-2 and CeMRT-1. My studies revealed that CePOT-1 acts as a bridge to connect these single-stranded DNA-binding proteins with CeTEBP-1 and ceTEBP-2, C. elegans\u2019 telomeric dsDNA-binding proteins. Taken together, my findings shed light on how C. elegans shelterin assembles at chromosome ends.\r\n\r\nThe second part of my thesis involves MEICEN, a testis-specific protein essential for male fertility. Centrosomes are organelles that play several major roles during mitosis and meiosis, including the formation of the bipolar spindle during mitosis and the formation of cilia and flagella. In sperm, remodeled centrosomes, called basal bodies, anchor the sperm flagellum to the sperm head. Centrins are proteins fundamental to centrosome assembly and duplication. Of the four mammalian centrins, centrin 1 is specifically expressed in testes and is essential for male fertility. \r\n\r\nOur collaborators, the Shibuya lab, identified MEICEN as a novel, testes-specific regulator of centrosome dynamics and sperm tail maturation that binds centrin and is essential for male fertility. Meicen knockout mice display irregular centrin 1 localization, which results in sperm tail defects. Yet how MEICEN binds centrin during meiosis was unknown. As part of my doctoral studies, I used SEC-MALS to reveal that MEICEN homodimerizes to bind a total of sixteen centrin molecules. I then solved the crystal structure of the MEICEN-centrin 1 complex to provide the structural basis of an interaction critical for spermatogenesis. Finally, I introduced mutations at the MEICEN-centrin interface to demonstrate that it abrogates the MEICEN-centrin interaction. Overall, our findings inspire a model in which MEICEN acts as a storage system for centrin to limit its over-accumulation at meiotic centrosomes, preventing their overduplication.", "occurrence_notes":null, "guid":"142316-21890509@events.umich.edu", "permalink":"http:\/\/events.umich.edu\/event\/142316", "building_id":"1005169", "building_name":"Biological Sciences Building", "campus_maps_id":"631", "room":"1010", "location_name":"Biological Sciences Building", "has_livestream":0, "cost":"", "tags":["Biology","Bsbsigns","Dissertation","Dissertation Defense"], "website":"https:\/\/lsa.umich.edu\/mcdb", "sponsors":[ { "group_name":"Department of Molecular, Cellular, and Developmental Biology", "group_id":"3755", "website":"" } ], "image_url":"https:\/\/events.umich.edu\/media\/attachments\/2025\/12\/event_142316_original-1.png", "styled_images":{ "event_thumb":"https:\/\/events.umich.edu\/media\/cache\/event_thumb\/media\/attachments\/2025\/12\/event_142316_original-1.png", "event_large":"https:\/\/events.umich.edu\/media\/cache\/event_large\/media\/attachments\/2025\/12\/event_142316_original-1.png", "event_large_2x":"https:\/\/events.umich.edu\/media\/cache\/event_large_2x\/media\/attachments\/2025\/12\/event_142316_original-1.png", "event_large_lightbox":"https:\/\/events.umich.edu\/media\/cache\/event_large_lightbox\/media\/attachments\/2025\/12\/event_142316_original-1.png", "group_thumb":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_thumb\/media\/attachments\/2025\/12\/event_142316_original-1.png", "group_thumb_square":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_thumb_square\/media\/attachments\/2025\/12\/event_142316_original-1.png", "group_large":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_large\/media\/attachments\/2025\/12\/event_142316_original-1.png", "group_large_lightbox":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_large_lightbox\/media\/attachments\/2025\/12\/event_142316_original-1.png", "event_large_crop":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_large_crop\/media\/attachments\/2025\/12\/event_142316_original-1.png", "event_list":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_list\/media\/attachments\/2025\/12\/event_142316_original-1.png", "event_list_2x":"https:\/\/events.umich.edu\/media\/cache\/event_list_2x\/media\/attachments\/2025\/12\/event_142316_original-1.png", "event_grid":"https:\/\/events.umich.edu\/media\/cache\/event_grid\/media\/attachments\/2025\/12\/event_142316_original-1.png", "event_grid_2x":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_grid_2x\/media\/attachments\/2025\/12\/event_142316_original-1.png", "event_feature_large":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_feature_large\/media\/attachments\/2025\/12\/event_142316_original-1.png", "event_feature_thumb":"https:\/\/events.umich.edu\/media\/cache\/event_feature_thumb\/media\/attachments\/2025\/12\/event_142316_original-1.png" }, "occurrence_count":1, "first_occurrence":21890509 } , "137853-21880916": { "datetime_modified":"20251211T120023", "datetime_start":"20251211T163000", "datetime_end":"20251211T173000", "has_end_time":1, "date_start":"2025-12-11", "date_end":"2025-12-11", "time_start":"16:30:00", "time_end":"17:30:00", "time_zone":"America\/Detroit", "event_title":"Crafting Meeting", "occurrence_title":"", "combined_title":"Crafting Meeting", "event_subtitle":"", "event_type":"Other", "event_type_id":"22", "description":"All are welcome to join us every Thursday from 4:30-5:30p for our crafting meeting! All skills are welcome with plenty of teachers and projects to start each week. If you have more questions, please DM us on Instagram or email our Monday meeting lead Calli:callil@umich.edu\r\nTime: 4:30-5:30 pm\r\nLocation:\u00a0North Campus\u00a0Duderstadt Design Lab 1\r\nNonprofit Website:\u00a0vipsfund.org\r\nInstagram:\u00a0@vipsfund", "occurrence_notes":null, "guid":"137853-21880916@events.umich.edu", "permalink":"http:\/\/events.umich.edu\/event\/137853", "building_id":"", "building_name":"", "campus_maps_id":"", "room":"", "location_name":"Duderstadt Design Lab 1", "has_livestream":0, "cost":"", "tags":[], "website":"https:\/\/maizepages.umich.edu\/event\/11457707", "sponsors":[ { "group_name":"Maize Pages Student Organizations", "group_id":"2390", "website":"" } ], "image_url":"https:\/\/events.umich.edu\/media\/attachments\/2025\/12\/event_137853_original-439.png", "styled_images":{ "event_thumb":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_thumb\/media\/attachments\/2025\/12\/event_137853_original-439.png", "event_large":"https:\/\/events.umich.edu\/media\/cache\/event_large\/media\/attachments\/2025\/12\/event_137853_original-439.png", "event_large_2x":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_large_2x\/media\/attachments\/2025\/12\/event_137853_original-439.png", "event_large_lightbox":"https:\/\/events.umich.edu\/media\/cache\/event_large_lightbox\/media\/attachments\/2025\/12\/event_137853_original-439.png", "group_thumb":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_thumb\/media\/attachments\/2025\/12\/event_137853_original-439.png", "group_thumb_square":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_thumb_square\/media\/attachments\/2025\/12\/event_137853_original-439.png", "group_large":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_large\/media\/attachments\/2025\/12\/event_137853_original-439.png", "group_large_lightbox":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_large_lightbox\/media\/attachments\/2025\/12\/event_137853_original-439.png", "event_large_crop":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_large_crop\/media\/attachments\/2025\/12\/event_137853_original-439.png", "event_list":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_list\/media\/attachments\/2025\/12\/event_137853_original-439.png", "event_list_2x":"https:\/\/events.umich.edu\/media\/cache\/event_list_2x\/media\/attachments\/2025\/12\/event_137853_original-439.png", "event_grid":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_grid\/media\/attachments\/2025\/12\/event_137853_original-439.png", "event_grid_2x":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_grid_2x\/media\/attachments\/2025\/12\/event_137853_original-439.png", "event_feature_large":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_feature_large\/media\/attachments\/2025\/12\/event_137853_original-439.png", "event_feature_thumb":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_feature_thumb\/media\/attachments\/2025\/12\/event_137853_original-439.png" }, "occurrence_count":1, "first_occurrence":21880916 } }