Université de Fribourg

Medicine in the fourth dimension

R.Cederroth, Christopher ; Albrecht, Urs ; Bass, Joseph ; Brown, Steven A. ; Dyhrfjeld-Johnsen, Jonas ; Gachon, Frederic ; Green, Carla B. ; Hastings, Michael H. ; Helfrich-Förster, Charlotte ; B.Hogenesch, John ; Lévi, Francis ; Loudon, Andrew ; B.Lundkvist, Gabriella ; H.Meijer, Johanna ; Rosbash, Michael ; S.Takahashi, Joseph ; Young, Michael ; Canlon, Barbara

In: Cell Metabolism, 2019, vol. 30, no. 2, p. 238–250

The importance of circadian biology has rarely been considered in pre-clinical studies, and even more when translating to the bedside. Circadian biology is becoming a critical factor for improving drug efficacy and diminishing drug toxicity. Indeed, there is emerging evidence showing that some drugs are more effective at nighttime than daytime, whereas for others it is the opposite. This...

Université de Fribourg

Circadian control of DRP1 activity regulates mitochondrial dynamics and bioenergetics

Schmitt, Karen ; Grimm, Amandine ; Dallmann, Robert ; Oettinghaus, Bjoern ; Restelli, Lisa Michelle ; Witzig, Melissa ; Ishihara, Naotada ; Mihara, Katsuyoshi ; Ripperger, Jürgen A. ; Albrecht, Urs ; Frank, Stephan ; Brown, Steven A. ; Eckert, Anne

In: Cell Metabolism, 2018, vol. 27, no. 3, p. 657-666.e5

Mitochondrial fission-fusion dynamics and mitochondrial bioenergetics, including oxidative phosphorylation and generation of ATP, are strongly clock controlled. Here we show that these circadian oscillations depend on circadian modification of dynamin-related protein 1 (DRP1), a key mediator of mitochondrial fission. We used a combination of in vitro and in vivo models, including human skin...

Université de Fribourg

NONO couples the circadian clock to the cell cycle

Kowalska, Elzbieta ; Ripperger, Jürgen A. ; Hoegger, Dominik C. ; Bruegger, Pascal ; Buch, Thorsten ; Birchler, Thomas ; Mueller, Anke ; Albrecht, Urs ; Contaldo, Claudio ; Brown, Steven A.

In: Proceedings of the National Academy of Sciences - PNAS, 2013, vol. 110, no. 5, p. 1592-1599

Mammalian circadian clocks restrict cell proliferation to defined time windows, but the mechanism and consequences of this interrelationship are not fully understood. Previously we identified the multifunctional nuclear protein NONO as a partner of circadian PERIOD (PER) proteins. Here we show that it also conveys circadian gating to the cell cycle, a connection surprisingly important for...

Université de Fribourg

Distinct roles of DBHS family members in the circadian transcriptional feedback loop

Kowalska, Elzbieta ; Ripperger, Jürgen A. ; Muheim, Christine ; Maier, Bert ; Kurihara, Yasuyuki ; Fox, Archa H. ; Kramer, Achim ; Brown, Steven A.

In: Molecular and Cellular Biology, 2012, p. -

Factors interacting with core circadian clock components are essential to achieve transcriptional feedback necessary for metazoan clocks. Here we show that all three members of the Drosophila Behavior Human Splicing (DBHS) family of RNA-binding proteins play a role in the mammalian circadian oscillator, abrogating or altering clock function when overexpressed or depleted in cells. Although these...

Université de Fribourg

The period length of fibroblast circadian gene expression varies widely among human individuals

Brown, Steven A. ; Fleury-Olela, Fabienne ; Nagoshi, Emi ; Hauser, Conrad ; Juge, Cristiana ; Meier, Christophe A. ; Chicheportiche, Rachel ; Dayer, Jean-Michel ; Albrecht, Urs ; Schibler, Ueli

In: PLoS Biology, 2005, vol. 3(10), p. e338

Mammalian circadian behavior is governed by a central clock in the suprachiasmatic nucleus of the brain hypothalamus, and its intrinsic period length is believed to affect the phase of daily activities. Measurement of this period length, normally accomplished by prolonged subject observation, is difficult and costly in humans. Because a circadian clock similar to that of the suprachiasmatic...