Characterizing structure and function of the bone marrow monocyte niche during fasting

• Applicants: Professorin Dr. Anja Erika Hauser; Professor Dr. Stefan Jordan
• Subject Area: Nutritional Sciences ; Immunology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 573470857

Increasing evidence supports the health-promoting effects of fasting. Gaining a deeper understanding of the underlying cellular and molecular mechanisms could inform the development of novel therapies for the prevention and treatment of chronic inflammatory diseases. We and others have previously shown that inflammatory monocytes are depleted from the bloodstream and accumulate in the bone marrow during fasting. Moreover, fasting alters the inflammatory profile of monocytes isolated from the bone marrow. However, the role of the bone marrow niche in regulating monocyte homeostasis and function during fasting remains poorly understood. In this project, we aim to gain comprehensive insights into (1) the structure and function of the bone marrow monocyte niche during fasting. To achieve this, we will apply advanced imaging technologies to identify and characterize the molecular and cellular microenvironments where monocytes, which are recruited from the bloodstream during fasting, reside. We will use multiplexed immunofluorescence histology and spatial transcriptomics to visualize microanatomical structures and delineate the cellular composition of the monocyte niche. In addition, we will track monocyte recruitment using intravital microscopy and map their three-dimensional distribution in the bone marrow using light sheet fluorescence microscopy. To understand how fasting-associated changes in monocyte gene expression are shaped by the niche, we will perform single-cell transcriptomic analyses and investigate the functional diversity of endothelial cells and pericytes/mesenchymal stromal cells. We will also explore the metabolic landscape of the bone marrow during fasting using NAD(P)H fluorescence lifetime imaging (FLIM) and spatial metabolomics. Furthermore, we will investigate (2) the functional relevance of the bone marrow niche in fasting-induced improvement of inflammatory disease. Using genetic tools, we will selectively disrupt niche-specific signals and factors, such as leptin receptor signaling and CCL2 production, and prevent monocyte recruitment to the bone marrow in a preclinical model of multiple sclerosis. We will comprehensively assess disease progression on molecular, cellular, and clinical levels. In summary, this collaborative project aims to define the cellular composition and functional role of the bone marrow monocyte niche during fasting. In the long term, our findings may contribute to the development of innovative therapeutic strategies for inflammatory diseases.

• DFG Programme: Research Grants