Ústav molekulární genetiky AV ČR, v. v. i.
Supervisor
António Pires da Silva Baptista
Project description
Immune tolerance involves self-reactive T cell deletion in the thymus, and peripheral constraint of self-reactive escapees by regulatory T cells (Tregs). The latter occurs mostly in secondary lymphoid organs such as lymph nodes, where Tregs actively limit self-reactive T cell activation by stealing of IL2. We have shown that lymph node fibroblastic reticular cells (FRCs) mediate intranodal Treg maintenance via MHC-II-dependent antigen presentation. In this project, we aim to 1) unravel the molecular mechanisms that determine MHC-II expression by FRCs; 2) determine which self-antigens are presented by FRCs (examining possible region-specific patterns of self-antigen presentation); and 3) determine the influence of immune activation in FRC MHC-II and self-antigen expression.
Candidate profile
This research involves mouse studies (surgery and adoptive cell transfer), wet-lab techniques (cell culture, flow cytometry and imaging), and analysis of sequencing and spatial data. The candidate is expected to have basic knowledge of bioinformatics (coding in R).
Suggested reading
Supervisor
António Pires da Silva Baptista
Project description
Lymphoid-myeloid crosstalk and cooperation are essential for host protection against infection. Involving multiple signaling pathways, this communication is thought to involve sensing of infection by myeloid cells which in turn activate lymphocytes, followed by feedback regulation of the myeloid response by the activated lymphocytes. Notably, in the absence of infection, this communication is thought to be limited, with both lymphoid and myeloid compartments mostly behaving independently from each other. Here, using mice with multiple deficiencies in lymphoid cells, reconstitution approaches involving cellular transplantation, single-cell RNA sequencing and genetic screens we aim to 1) determine the influence of lymphoid cells in quantitative and qualitative myeloid cell homeostasis; 2) determine the signaling pathways involved in setting the appropriate homeostatic lymphocyte-myeloid balances; and 3) determine how myeloid cells „raised“ in the absence of lymphocyte conditioning recognize and respond to infectious stimuli.
Candidate profile
This research involves mouse protocols (adoptive cell transfers, infections), wet-lab techniques (cell culture, genetic editing, flow cytometry and imaging), and analysis of sequencing data. The candidate is expected to have basic knowledge of mouse handling and genetics.
Suggested reading
