Biological rhythms with a period of about 24 hours are called circadian rhythms (from Latin circa dies, meaning "about a day"). Circadian rhythms exist at all levels of complexity, from gene expression to rhythms in physiology, metabolism, and behavior. They are generated by an internal timing system - an endogenous circadian clock - that allows organisms to anticipate daily changes in their environment. Light acts as the primary stimulus to synchronize the internal clock with the external world. In mammals, circadian clocks have been found in almost every cell, but they are organized hierarchically: A tiny brain structure, the suprachiasmatic nucleus (SCN) of the hypothalamus, is known to be the main pacemaker. Specialized neurons in the retina sense light and relay this information to the SCN via the retinohypothalamic tract. Peripheral clocks in other tissues are synchronized by the SCN and are responsible for regulating organ-specific rhythms in physiology and metabolism.
Over the past three decades, the molecular mechanism of circadian rhythm generation has been uncovered and the associated genes and gene variants have been identified. It is now clear that synchronization between endogenous circadian and exogenous environmental cycles is critical for health and well-being. However, modern life constantly challenges our internal clock, which can lead to circadian rhythm disruption. Today, it is undeniable that circadian rhythm disruption is associated with many common diseases, including sleep disorders, psychiatric and neurodegenerative diseases, metabolic and cardiovascular disorders, immune system dysfunctions, as well as cancer. The description of the underlying mechanisms, however, has only just begun.
Our group is engaged in understanding the molecular basics of the circadian clockwork in mammals and their impact on physiological and behavioral processes. We are studying the regulation of intra- and intercellular processes which generate high-amplitude circadian oscillations with biochemical, genetic, molecular- and cell-biological methods. A second major goal of our laboratory is to use the findings of chronobiology for the benefit of patients and thus promote the emerging field of "Circadian Medicine".
Ongoing projects in the lab include the characterization of molecular and cell biological mechanisms essential for the dynamics of circadian oscillations and thereby for physiology and behavior (funding by Deutsche Forschungsgemeinschaft TRR168
). For example, we have created novel reporter cells that allow us to study the dynamic behavior of clock proteins using single cell fluorescence microscopy to better understand the cell biology of the circadian clock. Together with theoretical biologists and mathematicians we develop theoretical concepts for the generation of molecular oscillations and synchronization of oscillating systems.
In addition, we have developed and are developing novel biomarker assays that allow easy and reliable readout of important characteristics of the human internal clock from a single biospecimen (e.g. blood or hair root cells). This "detecting the clock" has practical relevance on several levels: (i) Disease therapy might benefit significantly from an approach adapted to internal time (precision medicine). (ii) Disruption of the circadian clock by artificial light, shift work, travel across time zones, social jet lag, and daylight saving time changes has been associated with a variety of common diseases. This is why it is so important for disease prevention that internal time and external time match to prevent desynchronization between internal and external time and between organ clocks within the body. (iii) In addition to the therapeutic and preventive aspects, circadian diagnostics serves to reduce circadian rhythm disturbances in shift workers, e.g., by a shift schelule oriented to the chronotype, as well as to develop treatment strategies for patients with circadian rhythm disturbances.