Institute of Medical Psychology and Department of Molecular Biology

Project description:

The circadian clock is an endogenous timekeeping system that coordinates daily rhythms in physiology and behavior. At the cellular level, it is driven by a core transcriptional–translational feedback loop in which the transcription factor BMAL1 plays a central role. Although the core clock machinery is present in nearly all cell types, its transcriptional outputs differ markedly between tissues, enabling the temporal regulation of specialized cellular functions. The molecular mechanisms that generate this cell type specificity remain poorly understood. Our previous work identified, for the first time, homeodomain (HD) transcription factors as determinants of lineage-specific circadian transcriptional outputs in three different mouse tissues (doi.org/10.1038/s41556-026-02041-4). These findings suggest that HD factors connect the core circadian machinery with cell identity programs, directing BMAL1-dependent transcription towards tissue-specific functions.

This PhD project will extend the search for circadian regulatory HD factors to additional tissues and cell lineages. Using different cellular models and chromatin immunoprecipitation coupled with mass spectrometry (ChIP–MS) as a core technology, the PhD candidate will identify HD factors and associated protein complexes that interact with the circadian transcriptional machinery in a cell type-specific manner. Selected candidates will be characterized using complementary genomic, proteomic and functional approaches, including ChIP–seq, CUT&RUN, ATACseq, protein-protein interaction assays, gene-expression profiling and targeted perturbation. The project will determine whether HD transcription factors provide a general mechanism through which the circadian clock generates lineage-specific transcriptional programs across tissues.