Objective Modulating immune responses by shifting the balance of effector versus regulatory/memory T cells has significant potential as therapy for various autoimmune diseases and preventing organ transplant rejection. The mammalian Target Of Rapamycin Complex 1 (mTORC1) has diverse effects in T cells and can function to direct T cell fate. Direct mTORC1 inhibition provides potent immunosuppression but is associated with significant toxicity. Dissecting the mechanisms that account for the multiple mTORC1 effects on T cell differentiation is required to develop targeted therapies that provide desirable immunomodulatory effects without the toxicity associated with rapamycin treatment.The function of activated T cells is closely linked to their elevated metabolic state. Thus, inhibition of T cell metabolism via disruption of glucose metabolism or amino acid availability can alter T cell function. mTORC1 activity is acutely sensitive to the metabolic cues and has established roles in regulating cellular metabolism in other systems, through the control of Hypoxia Inducible Factor 1α (HIF1α) and Sterol Response Element Binding Protein 1c (Srebp1c) transcriptional activity. Based on the hypothesis that mTORC1 integrates the control of T cell metabolism and differentiation via common pathways, our data reveals a dual role for mTORC1/HIF1α in controlling glucose metabolism and CD8 T cell function. Lipid metabolism, controlled by mTORC1/Srebp1c in other cellular systems, has also been linked to T cell differentiation. Preliminary results demonstrate that activated T cells contain active mTORC1/Srebp1c signaling and suggest mTORC1 activity controls Srebp1c target genes, supporting a potential role for mTORC1/Srebp1c in the control of T cell function. This project aims to characterize the role for mTORC1/Srebp1c in the activation, differentiation and function of T lymphocytes using complementary pharmacological and genetic approaches and using state of the art in vivo technologies. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencescell biologycell metabolismnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesbasic medicineimmunologyautoimmune diseasesnatural scienceschemical sciencesorganic chemistryamines Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2012-CIG - Marie-Curie Action: "Career Integration Grants" Call for proposal FP7-PEOPLE-2012-CIG See other projects for this call Funding Scheme MC-CIG - Support for training and career development of researcher (CIG) Coordinator THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD, OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN EU contribution € 100 000,00 Address COLLEGE GREEN TRINITY COLLEGE D02 CX56 DUBLIN 2 Ireland See on map Region Ireland Eastern and Midland Dublin Activity type Higher or Secondary Education Establishments Administrative Contact Deirdre Savage (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
