{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"L-Asparaginase II produced by S. Typhimurium inhibits T cell responses through hydrolysis of L-asparagine and suppression of metabolic reprogramming","metadata":[{"label":"dc.description.sponsorship","value":"This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree."},{"label":"dc.format","value":"Monograph"},{"label":"dc.format.medium","value":"Electronic Resource"},{"label":"dc.identifier.uri","value":"http://hdl.handle.net/11401/77635"},{"label":"dc.language.iso","value":"en_US"},{"label":"dc.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.abstract","value":"Salmonella enterica serovar Typhimurium (S. Typhimurium) are pathogenic bacteria that suppress T cell responses to avoid clearance by the immune system, yet the mechanisms that mediate this immunosuppression remain largely unknown. Our laboratory previously showed that L-Asparaginase II produced by S. Typhimurium inhibits T cell responses and mediates virulence. The goal of my dissertation research was to determine the mechanism by which L-Asparaginase II produced by S. Typhimurium inhibits T cell responses. As described in my dissertation, I have found that L-Asparaginase II of S. Typhimurium exhibits L-asparagine hydrolysis activity and that this activity is required for the inhibition of T cells. Furthermore, I have found that exogenous L-asparagine is a resource important for T cell function and that L-Asparaginase II-mediated deprivation of exogenous L-asparagine inhibits T cell responses through suppression of metabolic reprogramming. The suppression of T cell metabolism was characterized by the inhibition of mTOR signaling, autophagy, c-Myc expression and new protein synthesis required for the activation, proliferation and differentiation of na\u00efve T cells into effector T cells. These findings advance knowledge of a mechanism used by S. Typhimurium to delay onset of protective immune responses and thus have fundamental implications for understanding host interactions with bacterial pathogens."},{"label":"dcterms.available","value":"2017-09-20T16:53:07Z"},{"label":"dcterms.contributor","value":"Krug, Laurie"},{"label":"dcterms.creator","value":"Torres, AnnMarie"},{"label":"dcterms.dateAccepted","value":"2017-09-20T16:53:07Z"},{"label":"dcterms.dateSubmitted","value":"2017-09-20T16:53:07Z"},{"label":"dcterms.description","value":"Department of Genetics."},{"label":"dcterms.extent","value":"139 pg."},{"label":"dcterms.format","value":"Monograph"},{"label":"dcterms.identifier","value":"http://hdl.handle.net/11401/77635"},{"label":"dcterms.issued","value":"2014-12-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2017-09-20T16:53:07Z (GMT). No. of bitstreams: 1\nTorres_grad.sunysb_0771E_11720.pdf: 3056539 bytes, checksum: 17848ea29dc0fe24f205200934b63305 (MD5)\n Previous issue date: 1"},{"label":"dcterms.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.subject","value":"Microbiology"},{"label":"dcterms.title","value":"L-Asparaginase II produced by S. Typhimurium inhibits T cell responses through hydrolysis of L-asparagine and suppression of metabolic reprogramming"},{"label":"dcterms.type","value":"Dissertation"},{"label":"dc.type","value":"Dissertation"}],"description":"This manifest was generated dynamically","viewingDirection":"left-to-right","sequences":[{"@type":"sc:Sequence","canvases":[{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json","@type":"sc:Canvas","label":"Page 1","height":1650,"width":1275,"images":[{"@type":"oa:Annotation","motivation":"sc:painting","resource":{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/25%2F19%2F83%2F25198354251027155656397875158258275680/full/full/0/default.jpg","@type":"dctypes:Image","format":"image/jpeg","height":1650,"width":1275,"service":{"@context":"http://iiif.io/api/image/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/25%2F19%2F83%2F25198354251027155656397875158258275680","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}