Resetting of peripheral clocks

By the turn of the millennium, it became clear that circadian clocks operate in virtually every cell of the body, not just in the brain. To function coherently, these cellular clocks must be synchronized with the external environment and each other. This synchronization is achieved through a range of time cues.

But which signals participate in the resetting of peripheral clocks? Do all tissues respond similarly, or is there tissue-specificity in how clocks are reset (Manella et al., Proc. Natl. Acad.. Sci. USA, 2020), (Manella et al., Nature Metabolism, 2021)? And do different tissues communicate time information among themselves, and if so, how?

To address these fundamental questions, we use in vivo mouse models, organotypic tissue explants, and cell culture systems. In addition, we developed Circa-SCOPE, a high-throughput platform for testing multiple circadian resetting cues in parallel using live single-cell fluorescence microscopy (Manella et al., Nature Communications, 2021). This method has revealed features like non-additivity and “gold change” detection, providing novel insights into the logic of circadian entrainment (Manella et al., Proc. Natl. Acad.. Sci. USA, 2022).