Project Details
Projekt
Specialized mRNA translation is a mediator of T cells immunity
Applicant
Dr. Jonathan Bohlen
Subject Area
Immunology
Human Genetics
Cell Biology
Human Genetics
Cell Biology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 566926179
Regulation of mRNA translation is widespread and essential for cellular and organismal processes. However, its role in immunity remains poorly explored. Human T cells provide an excellent model to investigate this frontier in molecular immunology. They are readily available in sufficient quantities, can be stimulated in a physiologically relevant manner, and are genetically accessible. I propose to study translational control in T cells from healthy donors and patients with monogenic inborn errors affecting translation reinitiation. Specifically, I hypothesize that (I) translational regulation mediates specialized T cell functions, (II) T cell-specific 5’TOP mRNAs drive T cell function in an mTOR-dependent manner, and (III) MCTS1-dependent translation of ATF4 contributes to T cell function. My recent publication identifying X-linked recessive MCTS1 deficiency as a novel genetic cause of susceptibility to mycobacterial infections highlights the scientific significance and potential of these questions. To address these hypotheses, I outline a research program that leverages state-of-the-art molecular biology techniques to investigate translational control in T cells. The proposal is supported by extensive preliminary data, reducing the risk associated with these studies. This program will provide fundamental insights into regulated mRNA translation in T cells, pave the way for improved T cell function in cell therapies such as CAR T cells, and establish the foundation for my broader investigation into mRNA translation in human immunity.
DFG Programme
Emmy Noether Independent Junior Research Groups
International Connection
Belgium, China, Iran, Oman, USA
