Circadian rhythms: a theoretical and practical view on internal 24-hour timing

Achim Kramer
AG Chronobiologie Charité - Universitätsmedizin Berlin CharitéCrossOver, Virchowweg 6 Charitéplatz 1 D-10117 Berlin

Circadian clocks are endogenous oscillators that drive ~24-hour rhythms in physiology, metabolism and behaviour of almost all life on earth. Circadian clocks are found at all levels - from cells, tissues and organs to the entire organism. In mammals, the master circadian clock resides in the hypothalamic suprachiasmatic nuclei (SCN) and coordinates daily rhythms of sleep and wakefulness, core body temperature and hormone secretion (such as

cortisol, melatonin and many others). It is synchronized to Earth’s rotation primarily by light- dark cycles – a process called `entrainment’, which is crucial for an organisms’ fitness. Little

is known about which oscillator qualities determine entrainment, i.e. entrainment range, phase and amplitude. Using mathematical modelling combined with experimental studies we found that coupling among single cell oscillators governs fundamental properties of circadian clock systems. In addition, we will present our recent development that allows the assessment of the phase of human circadian rhythms by a single time-point measurement using machine-learning algorithms at high dimensional time-series data from human blood cell transcriptomes. Since the internal circadian phase of humans is different for each individual and does not correspond to external clock time, such a precision medicine tool (BodyTime) enabling the personalization of healthcare according to the patient’s circadian clock is urgently needed.