{"607207":{"#nid":"607207","#data":{"type":"event","title":"PhD Defense by Shilpa Choudhury","body":[{"value":"\u003Cp\u003EIn partial fulfillment of the requirements for the degree of\u0026nbsp;\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\u0026nbsp;\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\u003EShilpa Choudhury\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\u003E\u003Cstrong\u003EANALYSIS OF POST-TRANSLATIONAL MODIFICATIONS \u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EIN THE REGULATION OF CELL SIGNALING AND BEHAVIOR\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EMonday, July 2\u003Csup\u003End\u003C\/sup\u003E, 2018\u003C\/p\u003E\r\n\r\n\u003Cp\u003E1:00 PM\u003C\/p\u003E\r\n\r\n\u003Cp\u003EEBB Seminar Room (1005)\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EThesis Advisor:\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDr. Matthew P. Torres\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\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDr. Brian Hammer\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\u003EDr. Yury Chernoff\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\u003EDr. Amit Reddi\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\u003EDr. John Hepler\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDepartment of Pharmacology\u003C\/p\u003E\r\n\r\n\u003Cp\u003EEmory University\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EROLE OF Gg SUBUNIT AS A NEGATIVE FEEDBACK PHOSPHO-REGULATOR OF G-PROTEIN SIGNALING IN YEAST\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ESummary\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EHeterotrimeric G proteins, composed of Ga, Gb, and Gg subunits, are essential for converting extracellular chemical stimuli into appropriate intracellular responses. The principal mechanism of G protein signal transduction is highly conserved throughout eukaryotes, including yeast. Binding of extracellular signal to cell surface receptors activates G proteins through a well characterized process involving GTP binding on the Ga subunit, dissociation of the heterotrimeric complex into Ga and Gbg subunits, and activation of downstream effectors that elicit a response to the stimulus. As mediators between transmembrane receptors and intracellular effectors, heterotrimeric G proteins are well positioned to serve as PTM-mediated regulators of G-protein signaling. Indeed, three primary PTMs are essential for G proteins to function: N-terminal myristoylation and palmitoylation of Ga subunits, and C-terminal prenylation of Gg subunits, all three of which function to anchor heterotrimeric G proteins to the plasma membrane of cells. In this context, while the signaling roles of Ga and Gb subunits and the PTMs which occur on these subunits are widely identified; Gg subunits are thought to serve the limited role of a membrane anchor for its obligate partner Gb and no other regulatory role was known.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThis study highlights a previously unknown role of Gg subunit in the regulation of G-protein signaling mediated through phosphorylation of their N-terminal intrinsically disordered region. Using a yeast model organism, \u003Cem\u003ESaccharomyces cerevisiae\u003C\/em\u003E, that harbors a single canonical G-protein signaling system to regulate a yeast mating pathway, we have identified a novel phosphorylation-dependent regulatory role of Gg subunit in yeast (Ste18). Several unique discoveries have ensued that provide a foundation for future studies in mammalian systems, where G protein signaling serves as a major drug target for the treatment of human disease. First, Ste18 is dynamically phosphorylated in response to GPCR activation. Second, this phosphorylation event is dependent on a MAPK (Fus3), which is the ortholog of human Erk2. Third, Ste18 phosphorylation, in conjunction with phosphorylation of a Gbg effector scaffold protein (Ste5), negatively regulates activation of the yeast mating pathway that is responsible for phosphorylation-based activation of Fus3. Fourth, negative regulation by phosphorylated Ste18\/Ste5 is mechanistically achieved by reducing binding affinity between Gbg\/(Ste4\/18) and effector Ste5, which results in controlling the bulk rate of active signaling complex formation at the plasma membrane in response to a GPCR stimulus.\u0026nbsp; Fifth, Ste18\/Ste5 phosphorylation regulates the sensitivity of the yeast mating process by altering its switch-like behavior. I go on to demonstrate that Ste18 phosphorylation can be promoted by signals other than GPCR stimulation. Specifically, I show that Ste18 phosphorylation is also sensitive to osmotic stress and cell-cycle progression, both of which may represent cross-talk mediated responses that funnel through the aforementioned Ste18\/Ste5 regulatory mechanism. Together, these findings reveal that combinatorial phosphorylation of Ste18 and the Gbg effector protein (Ste5) constitute a dynamic regulatory module that mediates negative regulation of G protein signaling in yeast and provide a foundation for understanding similar mechanisms undergone in mammalian cells.\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":"ANALYSIS OF POST-TRANSLATIONAL MODIFICATIONS  IN THE REGULATION OF CELL SIGNALING AND BEHAVIOR"}],"uid":"27707","created_gmt":"2018-06-20 17:29:08","changed_gmt":"2018-06-20 17:29:08","author":"Tatianna Richardson","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2018-07-02T14:00:00-04:00","event_time_end":"2018-07-02T16:00:00-04:00","event_time_end_last":"2018-07-02T16:00:00-04:00","gmt_time_start":"2018-07-02 18:00:00","gmt_time_end":"2018-07-02 20:00:00","gmt_time_end_last":"2018-07-02 20:00:00","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":"174045","name":"Graduate students"},{"id":"78751","name":"Undergraduate students"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[],"email":[],"slides":[],"orientation":[],"userdata":""}}}