Structural Chronobiology

Structural biology of proteins involved in time-controlled
(Circalunar and Circadian) biological processes

Chronobiology has become an increasingly important research area. Not only do disturbed circadian rhythms in humans enhance a variety of diseases like sleeplessness, metabolic syndrome, diabetes and cancer, but also do circalunar rhythms control the function and fertility of entire (marine) ecosystems, which is very important for planet earth’s health and wealth.

Physiological processes that are regulated in a timely, periodic manner, like so-called circadian (daily) and circalunar (monthly) rhythms, can be found in all kingdoms of life. Synchronization of these processes to environmental light cues requires photosensors, such as the cryptochrome in Drosophila (dCry), a sensor for daylight, and a different cryptochrome (L-Cry) in the marine worm Platynereis dumerilii, which can sense moonlight as time cue for monthly synchronization of spawning activities. Beside the light sensing molecules, it is also necessary for the organisms to maintain a strictly regulated periodic inner clock. This often turns out to be a complex network of molecular interactions which we headed out to investigate in detail.

Using a highly intradisciplinary structural biology approach, we aim to elucidate the molecular mechanistic bases of circadian and circalunar oscillators and their synchronization to sunlight and moonlight. Our methodical approaches include the biochemical and biophysical analyses of molecular interactions, activities (e.g. light responses) and conformational dynamics of clock proteins as well as their structural analyses by X-ray crystallography and Cryo electron microscopy (Cryo-EM). These structural and molecular-mechanistic insights will pose new biological questions to be addressed by functional experiments in cell culture and living organisms.