Coordinating circadian clocks throughout development: from single cell to organ interactions

• Applicant: Professor Dr. Richard Kempter, since 5/2024
• Subject Area: Bioinformatics and Theoretical Biology ; Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 511886499

Circadian clocks are heritable pacemakers that have evolved as an adaption to predictable daily changes in light intensity and temperature. Virtually every cell in mammals generates rhythmic clock gene expression with a period of approximately a day through intracellular transcriptional-translational negative feedback loops. While much progress has been made to understand the cogs and levers of this single cellular clockwork, how these clocks coordinate at the tissue, organ and organismal level to ensure a proper system level functioning is much less understood. Interestingly, the intracellular rhythm generation as well as the orchestration of these clocks also plastically changes throughout development but the underlying mechanisms remain largely unknown. The overall goal of this project is to advance our mechanistic understanding about developmental changes in the vertical integration of circadian signaling from cells to tissues as well as the horizontal integration between organs. For this sake I study networked circadian systems at different layers of its hierarchical organization: How do intracellular as well as neuronal network properties change throughout development in the mammalian circadian core pacemaker, the hypothalamic suprachiasmatic nucleus (SCN)? How do single cellular clocks in peripheral tissues such as neuroblastoma, a developmental pediatric tumor, self-organize and how does this self-organization affect pharmacological treatments? When during development does the circadian system gains control over functions of the cardiovascular system? How do circadian as well as non-circadian properties of cardiorespiratory interactions change throughout development? To answer these questions I will apply an interdisciplinary approach that combines state-of-the-art data analysis techniques, bioinformatics, oscillator theory as well as data-driven dynamical systems modeling. This project will lead to a better understanding how emergent properties arising through coupled cell autonomous clocks shape tissue, organ and organismal system level functioning to cope with the demands in a daily and seasonally changing world. Results of this interdisciplinary endeavor have a high translational potential, relevant for different fields such as chronobiology, systems biology, medicine or theoretical physics.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Dr. Christoph Schmal, until 4/2024