Ueli Schibler

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

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.

Schibler and his colleagues have also studied mechanisms by which peripheral oscillators are synchronized within the body. In 2000, they conducted experiments on the effects of restricted feeding time on mice and observed that the phase of peripheral oscillators – but not that of the SCN – gradually adapted to imposed feeding-fasting rhythms within a week or two. 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.

In a 1998 study, Schibler and his team published a paper providing strong evidence for the existence of circadian clocks in mammalian 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.

Over 5 years from 1967 to 1972, Schibler pursued the study of biology, biochemistry, and chemistry at the University of Bern, approximately seventy kilometers from his hometown of Olten. At graduation, he was awarded a Diploma in Biology. Afterwards, he continued his education there, eventually receiving his PhD diploma with Latin Honors in 1975 for his work on ribosomal RNA in the context of vertebrate evolution. He then obtained a postdoctoral fellowship from the Swiss National Science Foundation and worked at the laboratory of Robert Perry, who was based at the Fox Chase Cancer Center in Philadelphia for two years. In 1978, he became a junior group leader at The Swiss Institute for Experimental Cancer Research. In 1981, he was promoted to the status of a group leader with tenure, where he remained for three years. Finally, in 1984, he obtained a full professorship at the Department of Molecular Biology at the University of Geneva, where he currently resides.

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.

Ueli Schibler was born in 1947 in Olten, a small town in Switzerland. His father was a sculptor who manufactured monuments, and his mother helped manage the family business. In 1972, Ueli Schibler married with Monika Schibler, who he met at the age of 19, and had a son and daughter. His son was born in Philadelphia in 1977 when Ueli was a postdoc at Fox Chase Cancer Center while his daughter was born in 1979, one year after they moved back to Switzerland. Currently, Ueli Schibler resides in Switzerland and works in University of Geneva as a professor at the Department of Molecular Biology. Monika and Ueli Schibler are now grandparents and have three grandchildren.