Scientific achievements Ueli Schibler

1 scientific achievements

1.1 evidence of circadian clocks in peripheral tissues

1.1.1 circadian rhythms in peripheral tissue persist during cell division


1.2 feeding rhythms strong zeitgebers peripheral clocks
1.3 rev-erbα major regulator of circadian clock

scientific achievements
evidence of circadian clocks in peripheral tissues

while @ department of molecular biology @ university of geneva, schibler s research team unexpectedly came across dbp, transcriptional regulatory protein expression found robustly circadian in liver. discovery prompted schibler , team further investigate role of circadian clocks in peripheral tissue.

in 1998 study, schibler , team published paper providing strong evidence existence of circadian clocks in mammalian peripheral tissue. study demonstrated immortalized rat fibroblasts , frozen in cell culture 25 years, still capable of expressing strong circadian rhythms. after initial serum-shock, both rat-1 fibroblasts , h35 hepatoma cells demonstrated cyclic mrna expression of clock genes rper1 , rper2, , rev-erbα, , clock controlled genes tef , dbp, period of 24 hours , phase relationship closely mimicking observed in rat liver cells in vivo.

circadian rhythms in peripheral tissue persist during cell division

in 2004 study provided further evidence existence of self-sustained, autonomous oscillators in peripheral tissue, schibler , colleagues found evidence interaction between circadian clock , timing of cell division. single-cell recordings revealed how circadian gene expression in fibroblasts persists during cell division, , how cell division can phase shift circadian cycle of dividing cells. due central role of period (per) , cryptochrome (cry) proteins in negative feedback loop of circadian clock, schibler , colleagues posited per-cry complex concentration determinant of phase of clock. when cell division frequency plotted against circadian time, yielded highly nonrandom distribution, suggesting gating mechanism of mitosis circadian clock

feeding rhythms strong zeitgebers peripheral clocks

schibler , colleagues have studied mechanisms peripheral oscillators synchronized within body. in 2000, conducted experiments on effects of restricted feeding time on mice , observed phase of peripheral oscillators - not of scn – gradually adapted imposed feeding-fasting rhythms within week or two. these results showed feeding time functions potent zeitgeber peripheral cells, not scn. schibler , colleagues posited scn can synchronize peripheral clocks imposing rest-activity cycles, in turn drive feeding-fasting cycles. however, in meantime discovered additional pathways involved in phase-resetting of peripheral clocks, such signaling glucocorticoid hormones, body temperature, , actin dynamics.

rev-erbα major regulator of circadian clock

in 2002, schibler , colleagues identified nuclear orphan receptor rev-erbα major regulator of expression of circadian gene bmal1 in both scn , peripheral tissues. bmal-1, heterodimer clock activates transcription of components of negative limb encoding per , cry repressor proteins. together, feedback loop of positive limb , effects on negative limb produce mammalian circadian rhythms in clock gene expression. rev-erbα , paralog rev-erbβ molecular links between these 2 feedback loops.