Intercellular coupling and synchronization between peripheral circadian clocks – InSync

InSync is a research project at the interface of mathematics, computation, and biology, with the objective to decipher intercellular synchronization mechanisms responsible for generating robust circadian rhythms in peripheral tissues. Correctly phased oscillations of cellular circadian clocks ensure a healthy response of peripheral organs to internal synchronizers and contribute to the robustness of the circadian timing system at the organismal level in the presence of often unfavorable external cues (irregular food intake, night-shift work, exposition to harmful chemicals).
Recent experimental evidence show that coherent circadian oscillations are maintained in peripheral organs independently of the brain’s master clock. Peripheral clocks are also subject to bidirectional interactions with the cell division cycle, as shown recently by one of InSync partners, an interaction playing important roles in organ homeostasis. To rebound on these recent advances, our project focuses on hepatocytes to study intercellular communication patterns at a multi-scale level: from cellular clock phases and amplitudes to their synchronization at the scale of a cell population.
Combining expertise in mammalian circadian biology, mathematical modeling and computational tool development, InSync introduces two original contributions: (i) hepatocyte spheroids will be produced to better recapitulate the physiological 3D environment of the cells and assess candidate paracrine signaling pathways; (ii) dynamical models for local coupling and spatio-temporal models for a population of cells will be developed to provide a multi-scale view of a network of coupled peripheral clocks.
By recreating an environment where liver physiology and common pathologies can be reliably investigated, project InSync will answer questions on the temporal coordination of the cells at the tissue and organ scales to later implement preventive or therapeutic strategies aiming at reinforcing circadian rhythms.