Immune synapse and intracellular signaling

Our group is placed at the Campus of the University in Madrid. We have all the infrastructure required for our projects (in the campus or in the near institutes in Madrid). We are a small group composed by two PhD students and one Master student/year. Nevertheless, we constitute a research line of the research group validated by the University "Lymphocyte Immunobiology" (https://www.ucm.es/microbiologia-1/920631-lymphocyte-immunobiology-i-12) with the highest rank in the evaluation period 2004-2017 of the Ministry of Economy and Competitiveness (MINECO). We are currently funded by MINECO and have established different international collaborations in basic and translational research (please visit publications in Pubmed).

Actin dynamics has been proposed to control T cell antigen scanning and sensitivity. TCR triggering results in the formation of the immunological synapse, a specialized adhesion where a dynamic three-dimensional supra molecular structure of cytoskeleton and cell membranes organise the space where intracellular signalling sustains T cell activation. Nonetheless the interplay between signalling compartmentalisation and the dynamics of the cytoskeleton and the endo- and plasma-membrane compartment is still barely understood. Also, the regulatory role of many actin regulators, or other molecular components of the cell, in scanning efficiency, the IS assembly, and the T cell activation is not completely understood or have not been studied yet. For example the participation of the majority of dual specific phosphatases in these processes has not been explored. Base on previous data obtained by our group, the general objective of DST is to understand how the dual specific phosphatases "Phosphatases of regenerating liver (PRLs)", Slingshots, MTMR2, and the MAPK phosphatase DUSP8 participate in and are, in turn, regulated by the dynamic cytoskeleton and cell membranes during the activation of T cells. By combining gain-of-function and loss-of-function approaches with methods for measuring both, the real-time molecular dynamics (including reaction kinetics) and the activation of T cells, DST will study i) the regulatory mechanisms and delivery of PRLs at the IS, ii) the role of the cytoskeleton in the mobility properties of these DSPs at the IS, iii) the role of these DSPs in lymphocyte responses. DST will establish molecular bases of the T cell immune response. We expect the generated data to be useful for future translational and clinical research.

Curriculum vitae (including three referees)<br />Letter of motivation