TRR 418: Foundations of Circadian Medicine

The circadian clock is an endogenous timing program found throughout nature. It structures physiology and behavior according to time of day. 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 (Nobel Prize in Physiology or Medicine 2017). It is becoming increasingly 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. Such circadian rhythm disruption is associated with many common diseases, including sleep disorders, psychiatric and neurodegenerative diseases, metabolic and cardiovascular disorders, immune dysfunction, and cancer. The description of the underlying mechanisms, however, has only just begun. In addition, although it is known that the physiological state of the body differs significantly at different times of the day, little is known about the optimal treatment times for most commonly used drugs. The scientific goal of this consortium is to identify the overarching principles and characterize the underlying mechanisms linking the circadian clock and pathology in major organ and disease systems, and from this to develop and test evidence-based circadian medicine strategies for clinical application. We will use three principal approaches: (i) developing new diagnostic tools to enable personalized, clock-tailored interventions to establish circadian medicine as part of precision medicine (detecting the clock), (ii) improving or re-synchronizing disrupted rhythms by targeting the clock, and (iii) harnessing knowledge about physiological rhythms for time-of-day adapted treatment regimens (exploiting the clock). We have organized the consortium into three main areas - circadian immunology, circadian energy metabolism and circadian neuropsychiatry - not only to reflect specific expertise at the participating sites, but also to build on previous knowledge about the role of circadian rhythms in associated organ and disease systems. The three areas are intertwined, not just at the level of the standardized methododologies that we will develop and apply, but also in terms of their underlying mechanisms, for example, when exploring chrono-immunological mechanisms in nervous system diseases. Only a combined transdisciplinary effort will enable us to uncover common principles and mechanisms underlying circadian health. In the long term, we anticipate that understanding such principles and the consequences of circadian rhythm disruption will lead to a new era of personalized medicine, in which the state of the internal clock is considered an important factor not only in treatment decisions and success, but also in health promotion and disease prevention. With this consortium, we want to lay the foundations for this.

Projects and PIs

•A01 - Mechanisms of circadian vaccination responses in humans and mice (Prof. Dr. Leif E. Sander, Charité - Universitätsmedizin Berlin; Prof. Dr. Christoph Scheiermann, Université de Genève)

•A02 - Circadian regulation of light-induced disease activity in human and murine lupus (Prof. Dr. Markus Hoffmann and Prof. Dr. Tanja Lange, University of Luebeck)

•A03 - Molecular mechanisms of circadian clocks as therapeutic targets in mechanically ventilated intensive care unit patients (Prof. Dr. Nina H. Uhlenhaut, Technische Universität München (TUM); Prof. Dr. Martin Witzenrath, Charité - Universitätsmedizin Berlin)

•A04 - Internal circadian desynchronization and its impact on immune regulation (Prof. Dr. Simon Haas, Berlin Institute of Health (BIH); Prof. Dr. Achim Kramer, Charité - Universitätsmedizin Berlin)

•B01 - Circadian rhythms and chronotherapy in multiple sclerosis (Prof. Dr. Friederike C. Oertel, and Prof Dr. Friedemann Paul, Charité - Universitätsmedizin Berlin; Prof. Dr. Olga Ramich, Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DIfE))

•B02 - Circadian desynchronization and epigenetic alteration crosstalk on the development and resolution of metabolic dysfunction-associated steatohepatitis (Prof. Dr. Jens U. Marquardt, University of Luebeck; Prof. Dr. Maria Robles, Ludwig-Maximilian-Universität München)

•B03 - Dynamic chronotype and metabolic changes during puberty and their role in disease development (Prof. Dr. Peter Kühnen, Charité - Universitätsmedizin Berlin; Prof. Dr. Henrik Oster, University of Luebeck)

•B04 - Chronotherapy of metabolic dysfunction-associated steatotic liver disease (MASLD) (Leonardo De Assis, Ph.D., University of Luebeck; Prof. Dr. Münevver Demir, Charité - Universitätsmedizin Berlin)

•C01 - Individualized data-driven light intervention in intensive care unit patients (Prof. Dr. Felix Balzer and Prof. Dr. Claudia Spies, Charité - Universitätsmedizin Berlin)

•C02 - Circadian immune dysfunction in prodromal stages of Alzheimer‘s disease (Prof. Dr. Achim and Prof. Dr. Josef Kramer, Charité - Universitätsmedizin Berlin)

•C03 - Leveraging estimates of circadian disruption to support mental health and well-being (Prof. Dr. Inke König, University of Luebeck; Prof. Dr. Luisa K. Pilz, Charité - Universitätsmedizin Berlin)

•C04 - Circadian regulation of cognitive biases during adolescence (Prof. Dr. Sören Krach and Prof. Dr. Ines Wilhelm-Groch, University of Luebeck)

•C05 - Circadian rhythms of glucocorticoid and glutamatergic interactions in mood stabilit (Prof. Dr. Jonas Obleser and Prof. Dr. Henrik Oster, University of Luebeck)

•INF - Research data management and collaboration platform (Prof. Dr. Lisa Buchauer, Charité - Universitätsmedizin Berlin; Prof. Dr. Maija Poikela and Prof. Dr. Fabian Prasser, Berlin Institute of Health (BIH))

•MGK - Integrated Research Training Group RTG „Foundations of Circadian Medicine (Prof. Dr. Henrik Oster, University of Luebeck; Prof. Dr. Claudia Spies, Charité - Universitätsmedizin Berlin)

•S01 - Human chronotyping and circadian data analysis (Prof. Dr. Lisa Buchauer, Prof. Dr. Achim Kramer and Prof. Dr. Markus Ralser, Charité - Universitätsmedizin Berlin)

•Z - Central tasks (Prof. Dr. Achim Kramer, Charité - Universitätsmedizin Berlin)