Delineating the communication between endogenous clocks and their role in multimorbidity

Life on Earth evolved to function in harmony with geophysical phenomena such as the day-night cycles. Hence, many biological processes display endogenously generated 24-hour rhythms referred to as circadian rhythms.

These oscillations are controlled by a genetically encoded clock that exists in every organ, forming a circadian system of communicating clocks that are entrained by photic- and nutritional- cues.

Modern societies are characterized by 24-hour access to light and hypercaloric food that disrupts the circadian system (chronodisruption) and contributes to multiple chronic conditions.

In fact, about one-third of all adults suffer from two or more morbidities simultaneously (multimorbidity) and emerging knowledge suggests that there are causal links between them.

This project aims to dissect the underlying mechanisms between chronodisruption and multimorbidity with focus on the bidirectional relationship between metabolic- and mental- disease.

This will be achieved by first examining the effects of chronodisruption on metabolic and mental function and map the systemic molecular changes (transcriptomics, metabolomics and proteomics) in murine animal models. Secondly, the causal mechanisms will be dissected using genetic and pharmacological approaches in vitro and in vivo.

Finally, pre-clinical trials will be performed using therapies taking the temporal aspect into consideration (chronotherapies). The findings will highlight the temporal dimension of precision medicine.