Ueli Schibler

Ueli Schibler (born June 16, 1947) is a Swiss biologist, chronobiologist and a professor at the University of Geneva. His research has contributed significantly to the field of chronobiology and the understanding of circadian clocks in the body. Several of his studies have demonstrated strong evidence for the existence of robust, self-sustaining circadian clocks in the peripheral tissues.

Serendipitous discovery Schibler was thrust into the world of chronobiology on a single chance discovery. While examining transcription of serum albumin gene in the liver, they discovered a DNA Binding Protein (DBP) for the albumin promoter that happened to be rhythmic in its expression. While they initially thought that the underlying mechanism was the rhythmic secretion of hormones, it became clear that the rhythmic expression of DBP was driven instead by cell-autonomous oscillators that are entrained by the master clock in the Suprachiasmatic Nucleus (SCN). Schibler and his colleagues followed this line of inquiry into the field of chronobiology.

Current research A timing system with circadian clocks is closely related to all behaviors in mammals. Schibler is currently doing researches on how biological clock works. Schibler together with his research team in University of Geneva have developed a technique called "Synthetic Tandem Repeat PROMoter (STAR-PROM) screening" which can assist identify transcription factors and their functions in peripheral cells so that to figure out how circadian gene expression is governed rhythmically with regulatory mechanisms in cultured cells.

Scientific achievements

Evidence of circadian clocks in peripheral tissues While at the Department of Molecular Biology at the University of Geneva, Schibler's research team unexpectedly came across DBP, a transcriptional regulatory protein whose expression was found to be robustly circadian in the liver. This discovery prompted Schibler and his team to further investigate the role of circadian clocks in peripheral tissue. The study demonstrated that "immortalized rat fibroblasts", frozen in cell culture for 25 years, were still capable of expressing strong circadian rhythms. After an initial serum-shock, both rat-1 fibroblasts and H35 hepatoma cells demonstrated cyclic mRNA expression of clock genes rper1 and rper2, and Rev-Erbα, and the clock controlled genes Tef and Dbp, with a period of nearly 24 hours and a phase relationship closely mimicking those observed in rat liver cells in vivo.

Circadian rhythms in peripheral tissue persist during cell division In a 2004 study that provided further evidence for the existence of self-sustained, autonomous oscillators in the peripheral tissue, Schibler and his colleagues found evidence for interaction between the circadian clock and the timing of cell division. Single-cell recordings revealed how circadian gene expression in fibroblasts persists during cell division, and how cell division can phase shift the circadian cycle of the dividing cells. Due to the central role of Period (PER) and Cryptochrome (CRY) proteins in the negative feedback loop of the circadian clock, Schibler and colleagues posited the PER-CRY complex concentration to be the likely determinant of the phase of the clock. When cell division frequency was plotted against circadian time, this yielded a highly nonrandom distribution, suggesting a gating mechanism of mitosis by the circadian clock These results showed that feeding time functions as a potent Zeitgeber for peripheral cells, but not for the SCN. Schibler and colleagues posited that the SCN can synchronize peripheral clocks simply by imposing rest-activity cycles, which in turn drive feeding-fasting cycles. However, in the meantime they discovered additional pathways involved in the phase-resetting of peripheral clocks, such as signaling by glucocorticoid hormones, body temperature, and actin dynamics.

REV-ERBα is a Major Regulator of the Circadian Clock

In 2002, Schibler and his colleagues identified the nuclear orphan receptor REV-ERBα as the major regulator of expression of the circadian gene Bmal1 in both the SCN and peripheral tissues. BMAL-1, as a heterodimer with CLOCK activates the transcription of the components of the negative limb encoding PER and CRY repressor proteins. Together, the feedback loop of the positive limb and its effects on the negative limb produce the mammalian circadian rhythms in clock gene expression. REV-ERBα and its paralog REV-ERBβ are the molecular links between these two feedback loops.

Research experience Professor, University of Geneva (Since 1984) ”chercheur établi“, the Swiss Institute for Experimental Cancer Research in Epalinges (ISREC), Switzerland (1981–1984) ”chercheur associé“, the Swiss Institute for Experimental Cancer Research in Epalinges (ISREC), Switzerland (1978–1981) Visiting scientist, Dr R.P. Perry's laboratory (1977–1978) Postdoctoral fellow, Dr R.P. Perry's laboratory, Institute for Cancer Research, Fox Chase Center, Philadelphia (1975–1976)

Plenary and honorary lectures since 2007 2007: Werner Heisenberg Lecture, Bavarian Academy of Sciences and C. F. von Siemens Foundation, Munich, Germany EMBO Lecture, 15th P450 Conference, Bled, Slovenia Plenary Lecture, 9th European Congress of Endocrinology, Budapest, Hungary Plenary Lecture, IPSEN Meeting: The Evolving Biology of Growth and Metabolism, Lisbon, Portugal 2008: Pittendrigh Aschoff Lecture, 8th Meeting of the Society for Research on Biological Rhythms, Sandestin, USA 2009: Life Science Colloquium, Weizmann Institute, Rehovot, Israel 2010: Mendel Lecture, Augustinian Abbey in Brno, Czech Republic University Lecture, UT Southwestern Medical Center, Dallas, USA 2011: Keynote Address, EMBO Conference on Nuclear Receptors, Sitges, Spain Plenary Lecture, 10th Annual World Congress of the Human Proteome Organization, Geneva, Switzerland Plenary Lecture, XII Congress of the European Biological Rhythms Society, Oxford, UK Karl-Friedrich Bonhoeffer Lecture, Max Planck Institute for Biophysical Chemistry, Germany 2012: Kjeldgaard International Lecture in Molecular Biology, Aarhus University, Denmark Plenary Lecture, 14ème Réunion Commune des Sociétés Francophones de Néphrologie et de Dialyse, Geneva Plenary Lecture, 4th Congress European Academy of Paediatric Societies (EAPS), Istanbul, Turkey Plenary Lecture, SGED-SSED Annual Meeting, Berne Aschoff-Honma Prize Lecture, Sapporo, Japan 2013: Plenary Lecture, International Congress of Comparative Endocrinology, Barcelona, Spain Plenary Lecture, XIII Congress of the European Biological Rhythms Society, Munich, Germany 2014: Elected Richard M. Furlaud Distinguished Lecturer of 2013, Rockefeller University, New York, USA (Lecture held on February 14, 2014) "Servier Honorary Lecture" at the Open Ceremony of the World Congress of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, Seville, Spain

Notable papers

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