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Context-dependent Circadian Clock Synchrony across Cells and Tissues

Objective

Human physiology resonates with daily time through finely regulated 24-hour rhythms of hormone signals and temporally-gated metabolic peaks. These rhythms rely on an intricately organized network of circadian clocks, coordinated by a central pacemaker in the brain, and tuned by feeding, activity, or temperature cues.

Modern lifestyles in a 24/7 society disrupt this temporal organization, causing misalignment of body clocks with environmental cycles, increasing risk of cancer, metabolic and cardiovascular disease. Such misalignment can cause internal desynchrony, where clocks across organs or cells lose coordination.

Despite its increasing importance for human health, we lack quantitative frameworks to define and measure (de)synchrony across biological scales, particularly in humans, where time-resolved data are scarce.

CircaSync combines computational and experimental aims to provide new concepts for circadian medicine, delivering the first molecularly defined maps of circadian desynchrony in mice and humans.

Aim 1: New models for context-dependent circadian rhythms. We develop Chiral-ITy, a machine-learning model that translates static omics snapshots into interpretable circadian state maps, which are aligned across biological contexts (tissue type, cell state, disease and patient covariates).

Aim 2: Learning contextual internal desynchrony in humans at bulk and single cell scale. We leverage Chiral-ITy in human cohorts to quantify inter-organ desynchrony and its dependence on health covariates from multi-tissue transcriptomes. At the single-cell scale, we assess cellular synchrony and circadian clock states during liver disease progression.

Aim 3: Intestinal circadian desynchrony under mistimed feeding at single-cell resolution. We dissect the circadian organization and feeding-induced desynchrony of the intestine at cellular scale over multiple regulatory layers, and then engineer organoid arrays for live imaging and modeling of cell-type specific rhythms.

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2025-ADG

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Host institution

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 499 561,00
Address
BATIMENT CE 3316 STATION 1
1015 Lausanne
Switzerland

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Region
Schweiz/Suisse/Svizzera Région lémanique Vaud
Activity type
Higher or Secondary Education Establishments
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Total cost

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Beneficiaries (1)