Project Details
Projekt
Transcriptome-proteome relationship in neutrophils orchestrated by PU.1
Subject Area
Immunology
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 527581555
Neutrophils exert their immune functions with poor specificity. Therefore, failure to restrict a neutrophil reaction can cause serious damage to host tissue. Our published work has demonstrated that PU.1 suppresses the expression of hundreds of immune-response genes, thus restraining neutrophil activity on the transcriptional level. However, while transcriptional changes take a relatively long time (i.e., hours), neutrophils must react quickly to microbial invasions. Hence, immediate immune responses rely for the large part on already synthesized proteins. Through a combined proteomics and ubiquitomics approach, we have produced novel evidence indicating that PU.1 controls neutrophil functions on the level of protein turnover, via regulating components of the ubiquitin-proteasome system (UPS). Herein, we propose to thoroughly explore the PU.1-UPS connection. Moreover, because many UPS components are broadly expressed across many different tissues and cell types, we will study how the lineage-restricted transcription factor PU.1 regulates their expression in an immune-context dependent manner.
DFG Programme
Research Grants
