Reference number : GC-2017-Q1-02858, amendment number : , agreement type : G, recipient legal name : Baldwin, Troy (University of Alberta), recipient country : CA, recipient province : nan, recipient city : Alberta, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : T cells, an important component of the adaptive immune system, are derived from stem cells that undergo differentiation in an organ called the thymus. T cells can be broadly separated into two distinct lineages, &alpha;&beta; T cells and &gamma;&delta; T cells, based upon the class of T cell receptor (TCR) they express. These lineages arise from a bi-potent progenitor. While much is known regarding the signaling pathways required for development of &alpha;&beta; T cells, the role of these same signaling pathways in &gamma;&delta; T cell development is unclear. Furthermore, unlike most &alpha;&beta; T cells, &gamma;&delta; T cells possess the ability to rapidly produce cytokines. Signaling through the Ras pathway has been demonstrated to regulate the development of &gamma;&delta;-thymocytes. However, it is unclear which family of Ras activators, the Ras guanyl nucleotide releasing protein (RasGRP) or the Son of Sevenless (Sos) family is required for Ras activation in the context of gd-thymocyte development. Published data from us and others and our preliminary data suggest that RasGRP1 deficiency plays a critical role in &gamma;&delta; thymocyte development. We propose to test the hypothesis that RasGRP1 is a critical regulator of &gamma;&delta; thymocyte development and functional lineage specification. Furthermore, we will determine the mechanism underlying RasGRP1 regulation of gd-T cell development. This information will prove critical to further our long-term goal of understanding the molecular regulation of cell fate decisions., program purpose french : T cells, an important component of the adaptive immune system, are derived from stem cells that undergo differentiation in an organ called the thymus. T cells can be broadly separated into two distinct lineages, &alpha;&beta; T cells and &gamma;&delta; T cells, based upon the class of T cell receptor (TCR) they express. These lineages arise from a bi-potent progenitor. While much is known regarding the signaling pathways required for development of &alpha;&beta; T cells, the role of these same signaling pathways in &gamma;&delta; T cell development is unclear. Furthermore, unlike most &alpha;&beta; T cells, &gamma;&delta; T cells possess the ability to rapidly produce cytokines. Signaling through the Ras pathway has been demonstrated to regulate the development of &gamma;&delta;-thymocytes. However, it is unclear which family of Ras activators, the Ras guanyl nucleotide releasing protein (RasGRP) or the Son of Sevenless (Sos) family is required for Ras activation in the context of gd-thymocyte development. Published data from us and others and our preliminary data suggest that RasGRP1 deficiency plays a critical role in &gamma;&delta; thymocyte development. We propose to test the hypothesis that RasGRP1 is a critical regulator of &gamma;&delta; thymocyte development and functional lineage specification. Furthermore, we will determine the mechanism underlying RasGRP1 regulation of gd-T cell development. This information will prove critical to further our long-term goal of understanding the molecular regulation of cell fate decisions., agreement title english : Role of RasGRP1 in regulating lymphocyte development and function, agreement title french : Role of RasGRP1 in regulating lymphocyte development and function, agreement number : RGPIN, agreement value : 130000.0, agreement start date : 2017-05-10, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023), additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023), owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada