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| Name |
Schibler, Ueli |
| Location
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University of Geneva |
| Primary Field
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Medical Physiology and Metabolism |
| Secondary Field
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Cellular and Developmental Biology |
 Election Citation
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Schibler has studied the organization of the mammalian circadian timing system and discovered peripheral clocks and a novel feedback loop driving rhythmic gene expression. |
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Research Interests
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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. |
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