Circadian regulation of mass cell function

• Applicant: Professorin Maria S. Robles Martinez, Ph.D.
• Subject Area: Cell Biology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 583270475

The circadian clock is an internal timing system that temporally organizes cellular and tissue processes across the day. Oscillatory patterns in metabolism and behavior are not only observed under homeostatic conditions but also in certain pathologies that display pronounced symptomatic changes, such as allergic reactions. In this project, we aim to investigate how circadian function controls mast cells—the immune cells that trigger allergic responses—and whether this temporal regulation establishes the molecular basis for oscillations in symptoms, which often worsen at certain times of day. Here, we will i) characterize molecular oscillations and their impact on activation and mediator release in murine mast cells, while testing causality by disrupting clock function via Bmal1 deletion; ii) assess conserved cross-species circadian mechanisms by extending these analyses to diverse human mast cell models (primary from donor skin, iPSC-derived models, and established lines); iii) examine circadian-driven phosphorylation-dependent signaling pathways that give rise to time-of-day differences in degranulation; and iv) dissect the contribution of cell-intrinsic versus systemic circadian signals to mast cell function using in vivo isolated primary murine wildtype and Bmal1-deleted mast cells. To achieve these goals, we will use a complementary state-of-the-art molecular toolbox, including mass spectrometry-based quantitative proteomics and phosphoproteomics, transcriptomics and orthogonal functional assays by flow cytometry and ELISA. This multi-model approach will provide fundamental insights into how the circadian clock regulates mast cell activation and degranulation, uncovering the molecular basis of time-of-day-dependent allergic, anaphylactic signaling and mast cell-driven immune responses, and potentially identifying novel chronotherapeutic targets to enhance treatment precision, efficacy, and safety in the management of allergies and mast-cell–driven inflammation.

• DFG Programme: Research Grants