Ueli Schibler

Biosketch

Ueli Schibler, born in Olten, Switzerland, is a molecular biologist recognized for his work on tissue-specific and circadian gene expression in mammals. He is known for having developed an in vitro system for tissue-specific transcription and for having discovered that peripheral organs harbor self-sustained and cell-autonomous circadian oscillators. Moreover, his work revealed how these peripheral clocks are synchronized by the SCN master pacemaker, glucocorticoid hormones, feeding-fasting cycles, daily actin polymerization dynamics, and body temperature rhythms. Schibler studied biology at the University of Bern and obtained his Ph.D. in 1975. From 1975-1978 he worked as a postdoctoral fellow at the Fox Chase Cancer Center in Philadelphia and then joined the Swiss Institute for Experimental Cancer Research in Epalinges/Lausanne as a group leader. In 1984 he was appointed full professor at the Department of Molecular Biology, University of Geneva, and since 2016 he is professor emeritus at the same institution. Schibler is a member of the European Molecular Biology Organization, the European Academy of Sciences, the Swiss Academy of Medical Sciences, and the US National Academy of Sciences.

Research Interests

Ueli Schibler's laboratory was studying the molecular organization of the mammalian circadian timing system. By serendipity, his group discovered a leucine zipper transcription factor, dubbed DBP, whose accumulation in liver and other organs oscillates by more than two orders of magnitude in a daily fashion. Genetic loss-of-function studies revealed that DBP and its two paralogs TEF and HLF regulate neurotransmitter homeostasis in the brain and xenobiotic detoxification in the liver. In further studies, the Schibler lab demonstrated that cultured fibroblasts harbor self-sustained and cell-autonomous molecular oscillators. This finding led to the concept that the mammalian timing system has a hierarchical architecture, in which a central pacemaker in the suprachiasmatic nucleus synchronizes subsidiary clocks in peripheral tissues. Both central and peripheral oscillators are based on negative feedback loops in clock gene expression. The primary feedback loop is driven by CLOCK and BMAL1 activators and Cryptochrome and Period repressors. Schibler and coworkers identified a secondary feedback loop, established by REV-ERB and ROR nuclear orphan receptors, that is coupled to the primary feedback loop. They also contributed several studies showing that peripheral clocks can be synchronized by feeding-fasting cycles, glucocorticoid oscillations, body temperature rhythms, and daily actin polymerization/depolymerization dynamics.