Thesis supervisor: György Vámosi
Location of studies (in Hungarian): Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen Abbreviation of location of studies: DEBSI
Description of the research topic:
Interleukin-2 and -15 cytokines are important regulators of T cell function. They exert their effects via their heterotrimeric receptors. IL-2R and IL-15R are involved in lymphomas and autoimmune diseases, and a better understanding of their signaling may help designing more efficient receptor oriented therapies. IL-2 and -15 receptors share their signaling beta and gamma subunits, but have distinct alpha subunits. The mode of action of the two receptors is quite different: whereas all three IL-2R subunits are expressed by the same T cell, and the ligand is produced by the same or a neighboring cell, IL-15 acts mainly via transpresentation. In this process, a dendritic cell, macrophage or an epithelial cell expresses IL-15R alpha, which binds and presents IL-15 to the beta-gamma receptor dimer on a neighboring T cell, thereby inducing a signaling cascade. Besides several common functions, the two cytokines also have opposing roles: whereas at the end of the immune response IL-2 induces apoptosis via a mechanism called activation induced cell death, IL-15 is responsible for the long term survival of memory T cells. Probably the cytokine specific alpha receptor chains are responsible for the distinct cell fates. We plan to study the fate of the IL-15R alpha subunit, translocated to the T cell during transpresentation. We would like to identify its interaction partners, in particular define if it participates in transcription regulatory complexes directly in the nucleus. For our experiments we will use modern fluorescence microscopic, molecular biological and genomic tools. Our research may shed light on the molecular background of diverging cell fates induced by the two cytokines and may help the design of new target oriented therapies.
Required language skills: English intermediate level Number of students who can be accepted: 1