CRC TRR 332 - B03: Targeting cell-intrinsic mechanisms of neutrophil functions

Basic data for this project

Description

The response of neutrophils to microbial challenges involves both intracellular and extracellular immune pathways. The translation of external signals into appropriate transcriptional immune response programs is highly dependent on transcription factors. We have recently shown that the transcription factor PU.1 not only controls the transcription of immune genes, but also ensures immune defence by promoting the proteasomal degradation of the pre-synthesized immune proteome. Hence, our results have revealed a novel, pathogen- dependent, transcription-driven yet post-translationally controlled immune response network that offers new perspectives for neutrophil immunomodulation. We will build on these findings to interfere with cell-intrinsic control programs of neutrophil immune functions by targeting both the transcriptional and post-transcriptional axes. Our goal is to identify epigenetic and proteasomal pathways that are central to the immune activities of neutrophils and, as such, could be effective targets in immunotherapeutic settings. In addition, we investigate a novel mechanism by which the proteasome could induce immune status-dependent epigenomic remodelling via controlling the stabilization of the transcription factor ETS2 protein.