{"658206":{"#nid":"658206","#data":{"type":"event","title":"PhD Defense by LINA MANUELA JAY GARCIA","body":[{"value":"\u003Cp\u003EIn partial fulfillment of the requirements for the degree of\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDoctor of Philosophy in Biology\u003C\/p\u003E\r\n\r\n\u003Cp\u003EIn the\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ELINA MANUELA JAY GARCIA\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EWill defend her dissertation\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003ERole of a Ribosome-Associated Chaperone in Viability, Prion Propagation, and Stress Memory\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E09, June, 2022\u003C\/p\u003E\r\n\r\n\u003Cp\u003E11:00 AM\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EIn-person:\u003C\/strong\u003E\u0026nbsp;EBB Children\u0026rsquo;s Healthcare of Atlanta (CHOA) Seminar Room\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EVia Zoom: \u003C\/strong\u003E\u0026nbsp;\u003Ca href=\u0022https:\/\/gatech.zoom.us\/j\/91632007208\u0022 target=\u0022_blank\u0022\u003Ehttps:\/\/gatech.zoom.us\/j\/91632007208\u003C\/a\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003Cstrong\u003EThesis Advisor:\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EYury Chernoff, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ECommittee Members:\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EFrancesca Storici, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003ERaphael F. Rosenzweig, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003ELoren Williams, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Chemistry and Biochemistry\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EAnita Corbett, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Department of Biology\u003C\/p\u003E\r\n\r\n\u003Cp\u003EEmory University\u003C\/p\u003E\r\n\r\n\u003Cp\u003EABSTRACT: Misfolding occurs when proteins fail to fold into their proper functional state. Normally, most misfolded proteins refold or are targeted for degradation through a special network of chaperones in order to maintain cellular proteostasis. However, in some cases, misfolded proteins can form ordered fibrous aggregates called amyloids. Amyloids are generally associated with aging, with neurological disorders such as Alzheimer\u0026rsquo;s, Parkinson\u0026rsquo;s, and Huntington\u0026rsquo;s diseases, and with a variety of other disorders, such as Type II diabetes and atherosclerosis.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EYeast transmissible amyloids, termed yeast prions, are self-perpetuating heritable protein isoforms. Prion propagation in yeast is controlled by the chaperone machinery which includes Hsp104, Hsp70, and Hsp40 proteins. In this work, yeast \u003Cem\u003ESaccharomyces cerevisiae\u003C\/em\u003E is employed as a model to understand the molecular basis of how chaperones regulate the formation and propagation of amyloids. Here I focused on the ribosome-associated chaperone Ssb, a member of the Hsp70 family, encoded by two genes (\u003Cem\u003ESSB1\u003C\/em\u003E and \u003Cem\u003ESSB2\u003C\/em\u003E). This data indicates that during heat shock, Ssb is released from the ribosome and localized to the cytosol, interfering with Ssa, another Hsp70 protein, and impairing propagation of the prion [\u003Cem\u003EPSI\u003Csup\u003E+\u003C\/sup\u003E\u003C\/em\u003E]. Attachment of Ssb1 to the activation domain of the protein Gal4, containing strong nuclear localization signal (AD-Ssb1), causes the relocalization of Ssb to the nucleus, which leads to cytotoxicity and interference with propagation of [\u003Cem\u003EPSI\u003Csup\u003E+\u003C\/sup\u003E\u003C\/em\u003E], [\u003Cem\u003EURE3\u003C\/em\u003E], and [\u003Cem\u003EPIN\u003Csup\u003E+\u003C\/sup\u003E\u003C\/em\u003E], prion forms of the Sup35, Ure2 and Rnq1 proteins respectively. Moreover, relocation of the modified Ssb (AD-Ssb1) to the nucleus affects the function of Ssa directly or through a co-chaperone that is important for to Ssa function. I also found that deletion of \u003Cem\u003EZUO1\u003C\/em\u003E (coding for the Hsp40 cochaperone of Ssb) increases spontaneous formation of the prion [\u003Cem\u003EURE3\u003C\/em\u003E]. Moreover, in the absence of Ssb, increases the mitotic stability of the prion forms of Ure2 ([\u003Cem\u003EURE3\u003C\/em\u003E]) and Lsb2 ([\u003Cem\u003ELSB\u003Csup\u003E+\u003C\/sup\u003E\u003C\/em\u003E]) is increased, while normally non-heritable mnemon aggregates of Ste18, [\u003Cem\u003ESTE\u003Csup\u003E+\u003C\/sup\u003E\u003C\/em\u003E] become heritable. \u003Cem\u003EDe novo\u003C\/em\u003E formation of [\u003Cem\u003ELSB\u003Csup\u003E+\u003C\/sup\u003E\u003C\/em\u003E] and [\u003Cem\u003ESTE\u003Csup\u003E+\u003C\/sup\u003E\u003C\/em\u003E] is also increased in the absence of Ssb, especially during heat shock that leads to the massive accumulation of the [\u003Cem\u003ELSB\u003Csup\u003E+\u003C\/sup\u003E\u003C\/em\u003E] prions. These results indicate that Ssb is a general anti-prion regulator, whose impact is not restricted only to the [\u003Cem\u003EPSI\u003C\/em\u003E\u003Csup\u003E+\u003C\/sup\u003E] prion. In combination with the ribosome-associated chaperone complex (RAC), Ssb acts as a general modulator of cytosolic amyloid aggregation and can, directly or indirectly, repress prion generation and cure prions after they arise, counteracting prion toxicity. For further exploration of the interactions between chaperones, prions and ribosomal machinery, I have constructed a yeast [\u003Cem\u003EPSI\u003Csup\u003E+\u003C\/sup\u003E\u003C\/em\u003E] strain with a deletion of all rRNA genes from the chromosome (\u003Cem\u003Erdn1\u0026Delta;\u003C\/em\u003E), whose viability is dependent on the multicopy rRNA coding plasmid.\u0026nbsp; Overall, our work expands the current knowledge of the role ribosome apparatus and ribosome-associated chaperones in heritable protein aggregation.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":"","field_summary_sentence":[{"value":"Role of a Ribosome-Associated Chaperone in Viability, Prion Propagation, and Stress Memory"}],"uid":"27707","created_gmt":"2022-05-13 17:46:33","changed_gmt":"2022-05-13 17:46:33","author":"Tatianna Richardson","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2022-06-09T12:00:00-04:00","event_time_end":"2022-06-09T14:00:00-04:00","event_time_end_last":"2022-06-09T14:00:00-04:00","gmt_time_start":"2022-06-09 16:00:00","gmt_time_end":"2022-06-09 18:00:00","gmt_time_end_last":"2022-06-09 18:00:00","rrule":null,"timezone":"America\/New_York"},"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":"78761","name":"Faculty\/Staff"},{"id":"78771","name":"Public"},{"id":"78751","name":"Undergraduate students"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[],"email":[],"slides":[],"orientation":[],"userdata":""}}}