Objective Immunological memory is the basis of vaccination. This has been the subject of intense study, but the underlying cellular mechanisms regulating the generation and persistence of long-lived memory T cells (TM) remain largely undefined. Recently, it was shown that CD8+ T cell responses following bacterial infection could be manipulated by modulating cellular metabolism. Since then immunometabolism has emerged as one of the main frontiers in science, and my research is leading in this field. I recently demonstrated that the promotion of mitochondrial biogenesis (MB) and fatty acid oxidation (FAO) in CD8+ T cells during an immune response is crucial for their development into long-lived TM cells. An important regulator of MB and FAO is the peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1) family, and my preliminary data suggest that PGC-1 has a role in TM development. My proposal focuses on the novel concept that cellular metabolism and MB regulate CD8+ TM cell development. Importantly, this concept offers possibilities for pharmacological manipulation of TM formation.My objectives are (1) to determine the role of PGC-1 in mitochondrial metabolism during CD8+ TM development and (2) to investigate whether agents that promote MB enhance vaccine efficacy. For objective 1 I will generate CD8+ TM cells in vitro, and determine whether PGC-1 deficient CD8+ T cells have a defect in functional TM cell formation due to impaired mitochondrial metabolism. In addition, I will determine whether PGC-1 deficient CD8+ T cells will form functional TM cells in vivo. For objective 2 I will test whether MB-inducing drugs can improve TM cell development and function, both in vitro and in vivo. My project will provide insight into the mechanism of MB and TM development, and can lead to the development of novel vaccine strategies that could apply to a variety of diseases. Fields of science natural scienceschemical scienceselectrochemistryelectrolysismedical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines 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-2013-CIG - Marie-Curie Action: "Career Integration Grants" Call for proposal FP7-PEOPLE-2013-CIG See other projects for this call Funding Scheme MC-CIG - Support for training and career development of researcher (CIG) Coordinator ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM EU contribution € 93 750,00 Address MEIBERGDREEF 15 1105AZ Amsterdam Netherlands See on map Region West-Nederland Noord-Holland Groot-Amsterdam Activity type Higher or Secondary Education Establishments Administrative Contact Gulseren Yalvac (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data