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Ueli Schibler

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Ueli Schibler
Born(1947-06-16)June 16, 1947(age 77)
Olten, Switzerland
CitizenshipSwiss Citizen
Alma materUniversity of Bern
AwardsAschoff Honma Prize of the Honma Foundation,
Louis-Jeantet Prize for Medicine(2000)[1]
Scientific career
FieldsMolecular biology,Chronobiology
Notes

Ueli Schibler(born June 16, 1947)[2]is a Swiss biologist, chronobiologist and a professor at theUniversity 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.[3]

Schibler has studied the molecular biology of geneexpressionsand chronobiology since his serendipitous discovery of a protein expressed in a strong circadian fashion. He is also a current editor for several academic journals, such asPLoS Biology,EMBOReportsandJournal of Biological Rhythms.

Biography

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Early life and family

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Ueli Schibler was born in 1947 inOlten,a small town in Switzerland. His father was a sculptor who manufacturedmonuments,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 inPhiladelphiain 1977 when Ueli was a postdoc atFox Chase Cancer Centerwhile his daughter was born in 1979, one year after they moved back to Switzerland. Currently, Ueli Schibler resides in Switzerland and works inUniversity of Genevaas a professor at the Department ofMolecular Biology.Monika and Ueli Schibler are now grandparents and have three grandchildren.

Education and academic experiences

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Over 5 years from 1967 to 1972, Schibler pursued the study ofbiology,biochemistry,andchemistryat theUniversity of Bern,approximately seventy kilometers from his hometown ofOlten.At graduation, he was awarded a Diploma in Biology. Afterwards, he continued his education there, eventually receiving his PhD diploma withLatin Honorsin 1975 for his work onribosomal RNAin the context ofvertebrateevolution.[2]He then obtained a postdoctoral fellowship from the Swiss National Science Foundation and worked at the laboratory of Robert Perry, who was based at theFox Chase Cancer CenterinPhiladelphiafor two years. In 1978, he became a junior group leader atThe 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 theUniversity of Geneva,where he currently resides.[4]

Serendipitous discovery

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Schibler was thrust into the world ofchronobiologyon a single chance discovery. While examiningtranscriptionof serumalbumingene in the liver, they discovered a DNA Binding Protein (DBP) for the albuminpromoterthat happened to be rhythmic in its expression. While they initially thought that the underlying mechanism was the rhythmic secretion ofhormones,it became clear that the rhythmic expression of DBP was driven instead by cell-autonomousoscillatorsthat are entrained by the master clock in theSuprachiasmatic Nucleus(SCN). Schibler and his colleagues followed this line of inquiry into the field of chronobiology. [5]

Current research

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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 identifytranscription factorsand their functions in peripheral cells so that to figure out how circadian gene expression is governed rhythmically with regulatory mechanisms incultured cells.[6]

Scientific achievements

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Evidence of circadian clocks in peripheral tissues

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While at the Department of Molecular Biology at the University of Geneva, Schibler's research team unexpectedly came acrossDBP,atranscriptional regulatory proteinwhose expression was found to be robustlycircadianin the liver. This discovery prompted Schibler and his team to further investigate the role ofcircadian clocksin peripheral tissue.[2]

In a 1998 study, Schibler and his team published a paper providing strong evidence for the existence of circadian clocks in mammalian peripheral tissue.[3]The study demonstrated that "immortalized ratfibroblasts",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 cyclicmRNAexpression of clock genesrper1andrper2,andRev-Erbα,and the clock controlled genesTefandDbp,with a period of nearly 24 hours and a phase relationship closely mimicking those observed in rat liver cellsin vivo.[7]

Circadian rhythms in peripheral tissue persist during cell division

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In a 2004 study that provided further evidence for the existence of self-sustained, autonomous oscillators in the peripheral tissue,[8]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 duringcell division,and how cell division can phase shift the circadian cycle of the dividing cells.[9]Due to the central role of Period(PER)and Cryptochrome(CRY)proteins in thenegative feedback loopof the circadian clock, Schibler and colleagues posited the PER-CRY complex concentration to be the likely determinant of the phase of the clock.[10]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[9]

Feeding Rhythms are Strong Zeitgebers for Peripheral Clocks

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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 theSCN– gradually adapted to imposed feeding-fasting rhythms within a week or two.[11]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 byglucocorticoid hormones,[12]body temperature,[13]andactindynamics.[14]

REV-ERBα is a Major Regulator of the Circadian Clock

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In 2002, Schibler and his colleagues identified the nuclear orphan receptorREV-ERBαas the major regulator of expression of the circadian geneBmal1in both the SCN and peripheral tissues. BMAL-1, as aheterodimerwithCLOCKactivates the transcription of the components of the negative limb encodingPERandCRYrepressor 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 paralogREV-ERBβare the molecular links between these two feedback loops.[15][16]

Research experience

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Plenary and honorary lectures since 2007

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  • 2007:
  1. Werner Heisenberg Lecture, Bavarian Academy of Sciences and C. F. von Siemens Foundation, Munich, Germany
  2. EMBO Lecture, 15th P450 Conference, Bled, Slovenia
  3. Plenary Lecture, 9th European Congress of Endocrinology, Budapest, Hungary
  4. 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:
  1. Mendel Lecture, Augustinian Abbey in Brno, Czech Republic
  2. University Lecture, UT Southwestern Medical Center, Dallas, USA
  • 2011:
  1. Keynote Address, EMBO Conference on Nuclear Receptors, Sitges, Spain
  2. Plenary Lecture, 10th Annual World Congress of the Human Proteome Organization, Geneva, Switzerland
  3. Plenary Lecture, XII Congress of the European Biological Rhythms Society, Oxford, UK
  4. Karl-Friedrich Bonhoeffer Lecture, Max Planck Institute for Biophysical Chemistry, Germany
  • 2012:
  1. Kjeldgaard International Lecture in Molecular Biology, Aarhus University, Denmark
  2. Plenary Lecture, 14ème Réunion Commune des Sociétés Francophones de Néphrologie et de Dialyse, Geneva
  3. Plenary Lecture, 4th Congress European Academy of Paediatric Societies (EAPS), Istanbul, Turkey
  4. Plenary Lecture, SGED-SSED Annual Meeting, Berne
  5. Aschoff-Honma Prize Lecture, Sapporo, Japan
  • 2013:
  1. Plenary Lecture, International Congress of Comparative Endocrinology, Barcelona, Spain
  2. Plenary Lecture, XIII Congress of the European Biological Rhythms Society, Munich, Germany
  • 2014:
  1. Elected Richard M. Furlaud Distinguished Lecturer of 2013, Rockefeller University, New York, USA (Lecture held on February 14, 2014)
  2. "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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  • Balsalobre, A.; Damiola, F.; Schibler, U. (1998)."A serum shock induces circadian gene expression in mammalian tissue culture cells".Cell.93(6): 929–937.doi:10.1016/S0092-8674(00)81199-X.PMID9635423.[1][2][3]
  • McGinnis, W.; Levine, M. S.; Hafen, E.; Kuroiwa, A.; Gehring, W. J. (1984). "A conserved DNA sequence in homoeotic genes of the Drosophila Antennapedia and bithorax complexes".Nature.308(5958): 428–33.Bibcode:1984Natur.308..428M.doi:10.1038/308428a0.PMID6323992.(thehomeoboxpaper)
  • Han, Kyuhyung; Levine, Michael S.; Manley, James L. (1989). "Synergistic activation and repression of transcription by Drosophila homeobox proteins".Cell.56(4): 573–83.doi:10.1016/0092-8674(89)90580-1.PMID2563673.
  • Small, S; Blair, A; Levine, M (1992)."Regulation of even-skipped stripe 2 in the Drosophila embryo".The EMBO Journal.11(11): 4047–57.doi:10.1002/j.1460-2075.1992.tb05498.x.PMC556915.PMID1327756.
  • Arora, K; Levine, M S; O'Connor, M B (1994)."The screw gene encodes a ubiquitously expressed member of the TGF-beta family required for specification of dorsal cell fates in the Drosophila embryo".Genes & Development.8(21): 2588–601.doi:10.1101/gad.8.21.2588.PMID7958918.
  • Gachon, Frederic; Fonjallaz, Philippe; Damiola, Francesca; Gos, Pascal; Kodama, Tohru; Zakany, Joszef; Duboule, Denis; Petit, Brice; Tafti, Mehdi; Schibler, Ueli (2004)."The loss of circadian PAR bZip transcription factors results in epilepsy".Genes & Development.18(12): 1397–1412.doi:10.1101/gad.301404.PMC423191.PMID423191.

See also

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References

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  1. ^Louis-Jeantet Prize
  2. ^abc"Professeur Ueli Schibler, EMBO/EMBL Conference".
  3. ^abReppert, Steven; Weaver, David (29 August 2002). "Coordination of Circadian Timing in Mammals".Nature.418(6901): 935–941.Bibcode:2002Natur.418..935R.doi:10.1038/nature00965.PMID12198538.
  4. ^"Professeur Ueli Schibler, F1000 Prime Profile".
  5. ^Preitner N; Brown S; Ripperger J; Le-Minh N; Damiola F; Schibler U (25 June 2004).Molecular Clocks and Light Signalling.Novartis Foundation. John Wiley & Sons. p. 89.ISBN978-0-470-09082-4.
  6. ^"Identifying all factors modulating gene expression is actually possible, PHYS.ORG".
  7. ^Balsalobre, Aurélio; Damiola, Francesca; Schibler, Ueli (12 June 1998)."A Serum Shock Induces Circadian Gene Expression In Mammalian Tissue Culture Cells".Cell.93(6): 929–937.doi:10.1016/s0092-8674(00)81199-x.PMID9635423.
  8. ^Takahashi, Joseph; Hong, Hee-Kyung; Ko, Caroline; McDearmon, Erin (9 October 2008)."The genetics of mammalian circadian order and disorder: implications for physiology and disease".Nature Reviews Genetics.9(10): 764–775.doi:10.1038/nrg2430.PMC3758473.PMID18802415.
  9. ^abNagoshi, Emi; Saini, Camille; Bauer, Christoph; Laroche, Thierry; Naef, Felix; Schibler, Ueli (24 November 2004)."Circadian Gene Expression in Individual Fibroblasts: Cell-Autonomous and Self-Sustained Oscillators Pass Time to Daughter Cells".Cell.119(5): 693–705.doi:10.1016/j.cell.2004.11.015.PMID15550250.
  10. ^Bae, Kiho; Jin, Xiaowei; Maywood, Elizabeth; Hastings, Michael; Reppert, Steven; Weaver, David (May 2001)."Differential Functions of mPer1, mPer2, and mPer3 in the SCN Circadian Clock".Neuron.30(2): 525–536.doi:10.1016/S0896-6273(01)00302-6.PMID11395012.
  11. ^Damiola, Francesca; Le Minh, Nguyet; Preitner, Nicolas; Kornmann, Benoît; Fleury-Olela, Fabienne; Ueli, Schibler (9 October 2000)."Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus".Genes & Development.14(23): 2950–61.doi:10.1101/gad.183500.PMC317100.PMID11114885.
  12. ^Balsalobre, Aurélio; Brown, Steven; Marcacci, Lysiane; Tronche, Francois; Kellendonk, Christoph; Reichardt, Holger; Schütz, Günther; Schibler, Ueli (September 2000). "Resetting of Circadian Time in Peripheral Tissues by Glucocorticoid Signaling".Science.289(29): 2344–2347.doi:10.1126/science.289.5488.2344.PMID11009419.
  13. ^Brown, Steven; Zumbrunn, Gottlieb; Fleury-Olela, Fabienne; Preitner, Nicolas; Schibler, Ueli (17 September 2002)."Rhythms of Mammalian Body Temperature Can Sustain Peripheral Circadian Clocks".Cell.12(18): 1574–1583.doi:10.1016/S0960-9822(02)01145-4.PMID12372249.
  14. ^Gerber, Alan; Esnault, Cyril; Aubert, Gregory; Treisman, Richard; Pralong, Francois; Schibler, Ueli (31 January 2013)."Blood-Borne Circadian Signal Stimulates Daily Oscillations in Actin Dynamics and SRF Activity".Cell.152(3): 492–503.doi:10.1016/j.cell.2012.12.027.PMID23374345.
  15. ^Cho, Han; Zhao, Xuan; Hatori, Megumi; Yu, Ruth; Barish, Grant; Lam, Michael; Chong, Ling-Wa; DiTacchio, Luciano; Atkins, Annette; Glass, Christopher; Liddle, Christopher; Auwrex, Johan; Downes, Michael; Panda, Satchidananda; Evans, Ronald (29 March 2012)."Regulation of Circadian Behavior and Metabolism by Rev-erbα and Rev-erbβ".Nature.485(7396): 123–127.doi:10.1038/nature11048.PMC3367514.PMID22460952.
  16. ^Bugge, Anne; Feng, Dan; Everett, Logan; Briggs, Erika; Mullican, Shannon; Wang, Fenfen; Jager, Jennifer; Lazer, Mitchell (1 April 2012)."Rev-erbα and Rev-erbβ coordinately protect the circadian clock and normal metabolic function".Genes & Development.26(7): 657–667.doi:10.1101/gad.186858.112.PMC3323877.PMID22474260.
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