Objetivo In this project, I propose to characterize the influence of SteD, an effector of a globally important bacterial pathogen Salmonella enterica, on T cell development, and its potential therapeutic application. In the mouse model of S. enterica infection, the onset of the specific immune responses is delayed significantly in comparison to other bacterial pathogens. Recent work by the group of Prof. Holden, who is the supervisor of this project, a world leader in the field of Salmonella pathogenesis and the Director of the MRC Centre for Molecular Bacteriology and Infection (MRC-CMBI) at Imperial College London, identified SteD, an effector of the Type III Secretion System (T3SS) encoded by Salmonella pathogenicity island 2 (SPI-2), as the first example of a virulence factor that reduces surface-localised mature Major Histocompatibility Complex class II (MHCII) levels in Dendritic Cells. In addition, I have found an increased activation of T cells following infection of C57BL/6 mice with S. enterica serovar Typhimurium (STm) ΔsteD mutant in comparison to wild-type STm, thereby showing that SteD is an important modulator of adaptive immunity in vivo. SteD and/or its gene have a high chance of having therapeutic application. I also have obtained preliminary evidence indicating that SteD has additional functions in the manipulation of antigen-presenting cells. Therefore, I propose to use both the acute and chronic mouse models of Salmonella infection to further characterize the influence of SteD on T cell development. Furthermore, I will investigate the mechanistic and physiological significance of natural variation in the amino acid sequence of SteD among a broad range of S. enterica serovars, including the typhoid fever-causing human-adapted serovars Typhi and Paratyphi. Finally, I will explore the possible use of SteD in new formulations of DNA vaccines. These studies will provide important knowledge for the clinical application of this newly described T3SS effector. Ámbito científico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunologymedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccinesmedical and health sciencesclinical medicineoncologynatural scienceschemical sciencesorganic chemistryamines Programa(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Tema(s) MSCA-IF-2016 - Individual Fellowships Convocatoria de propuestas H2020-MSCA-IF-2016 Consulte otros proyectos de esta convocatoria Régimen de financiación MSCA-IF-EF-ST - Standard EF Coordinador IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE Aportación neta de la UEn € 195 454,80 Dirección SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON Reino Unido Ver en el mapa Región London Inner London — West Westminster Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 195 454,80