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Circa-SCOPE: high-throughput live single-cell imaging method for analysis of circadian clock resetting
Gal Manella1, Dan Aizik1, Rona Aviram1
1Department of Biomolecular Sciences, Weizmann Institute of Science, 7610001, Rehovot, Israel.
Nature Communications
|October 9, 2021
Summary
We developed Circa-SCOPE, a high-throughput assay to efficiently generate high-resolution Phase Transition Curves (PTCs) for circadian clocks. This method enables comprehensive analysis of circadian clock resetting cues.
Area of Science:
- Chronobiology
- Cellular Oscillators
- Biophysical Assays
Background:
- Circadian clocks are cell-autonomous oscillators responding to external cues.
- Phase Transition Curves (PTCs) reveal signal responses but are difficult to generate.
- Current PTC methods are low-throughput, laborious, and time-consuming.
Purpose of the Study:
- To develop an efficient, high-throughput assay for generating high-resolution PTCs.
- To enable comprehensive analysis of circadian clock resetting cues.
- To facilitate basic and translational research on circadian rhythms.
Main Methods:
- Developed Circadian Single-Cell Oscillators PTC Extraction (Circa-SCOPE) assay.
- Utilized continuous single-cell oscillation monitoring.
- Reconstructed full PTCs from a single culture after one intervention.
Main Results:
- Circa-SCOPE enables high-throughput, high-resolution PTC generation.
- Characterized pharmacological and blood-borne resetting cues.
- Demonstrated analysis across wide concentration ranges and high temporal resolution.
Conclusions:
- Circa-SCOPE is a powerful tool for circadian clock resetting cue analysis.
- The assay accelerates screening and comprehensive characterization of circadian responses.
- Valuable for both fundamental chronobiology and translational applications.

