Towards global phenotyping of circadian clocks from single samples

Virtually all differentiated cells in the human body possess a circadian oscillator that modulates temporal patterns of many key pathways of cellular metabolism. Collectively, the human body is a well synchronised network of cellular oscillators governed by the central pacemaker of the brain, the suprachiasmatic nuclei. Disruption of clock function on the cellular as well as on the organismal level has been shown to be associated with negative health consequences. For example, shift-workers with circadian disruption experience higher rates of metabolic disease as well as cancer, and the WHO has classed circadian disruption as a possible carcinogen. Inversely, there is evidence that cellular clock function is disrupted in cancer cells and has been suggested that this has an impact on disease progression and treatment success.

Importantly, methods to determine the clock status, for example, of a tumour from a single biopsy, are not yet available in the clinic. This project will establish (i) a new algorithm to generate realistic simulations of the clock and clock disruption, (ii) use the resulting synthetic data to improve and further develop methods to determine circadian clock phenotype from single samples, (iii) generate a user-friendly work-flow for the community, (iv) validate data and models in simple in vitro models, and seek to apply the resulting model on other publicly available data-sets.