Coordination of Circadian Oscillators in Organized Networks

• Applicant: Dr. Marta Del Olmo Somolinos
• Subject Area: Bioinformatics and Theoretical Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 571800473

Biological timing is fundamental across all living organisms. Mammalian metabolism, physiology, and behavior synchronize with the day/night cycle through cell-autonomous clocks distributed throughout the body. These clocks, although inherently noisy and heterogeneous at the single-cell level, organize to ensure coherent tissue-level oscillations. This proposal aims to understand how cells and tissues generate robust 24-hour rhythms and the mechanisms that ensure precise circadian outputs. While core clock gene mRNAs oscillate over the 24-hour cycle, significant cell-to-cell variability suggests that mRNA counts in a single cell likely cannot specify the cell’s circadian phase. Work Package 1 (WP1) investigates how cells mitigate noise present at the transcript level. Specifically, I will analyze the statistical properties of clock protein rhythms in single cells to explore whether they are more robust and could encode circadian phase information. Our recent findings on protein repressor stability varying over the circadian cycle suggest that these variations might filter mRNA noise, contributing to robust protein-level oscillations. WP2 focuses on characterizing oscillator properties and the coupling topology of the clock network in pancreatic islets. Clocks in α- and β-cells regulate diurnal insulin and glucagon secretion, ultimately orchestrating glucose homeostasis. Through advanced microscopy data analysis techniques and computational modeling, I aim to decipher how α- and β-cell clocks spatially and temporally exchange circadian information and how this spatiotemporal organization is disturbed in type 2 diabetes. In the final WP, I focus on the crosstalk between pancreatic islets and skeletal muscle, a key insulin-sensitive organ that secretes myokines like IL-6 to modulate metabolism locally and systemically. Different temporal profiles of IL-6 elicit varying responses in β-cells, influencing circadian interactions between muscle and pancreatic islets. WP3 aims to elucidate how β-cells discriminate between transient, chronic, and circadian IL-6 signals, and how the interplay of IL-6 and insulin signals shapes circadian function in both tissues. Ultimately, this interdisciplinary project integrates data science, bioinformatics, and mathematical modeling to explore circadian signaling from single cells to tissues and across organs in mammals. Collaboration with Prof. Charna Dibner’s lab at the University of Geneva - leading experts on β-cell and muscle clocks - will enable a productive synergy between theoretical and experimental approaches, where mathematical predictions can be directly tested. This interdisciplinary proposal will contribute to a deeper understanding of the strategies that ensure robust timekeeping in the mammalian circadian system, from single cells to coupled tissue structures.

• DFG Programme: Research Grants