| Daily fluctuations in biochemical, physiological
and behavioral phenomena are governed by endogenous circadian (~24
hour) clocks that can be synchronized (entrained) by external time
cues (zeitgebers), most notably the daily changes in light/dark
and temperature. This adaptive feature of circadian clocks enables
organisms to temporally align their physiology and behavior such
that they occur at biologically advantageous times during the day.
Malfunctions in the circadian timing system contribute to many human
disorders, including chronic sleep problems and affective disorders,
such as manic-depression. More recent evidence has indicated roles
for circadian clocks in cancer, cell-cycle progression, alcoholism,
long-term memory, mating, apoptosis and many signaling pathways.
The main goal of our laboratory is to understand the molecular
and biochemical bases of circadian clocks or pacemakers. To achieve
this goal, we are using the powerful genetics available in Drosophila
in combination with biochemical, molecular, proteomic, cell culture,
evolutionary, histochemical and whole-animal approaches. Much of
the research is focused on characterizing "clock proteins"
and understanding how they interact to form timekeeping devices
that can be synchronized by external cues and impart time-of-day
information to various cellular, physiological and behavioral programs.
Recent interests include the role of time-dependent phosphorylation
and its intersection with the proteasome pathway to produce daily
fluctuations in clock protein levels, a key event in the normal
progression of clocks. In addition, we are interested in understanding
how the dynamics of circadian clocks are adjusted by seasonal changes
in day length and temperature, a mechanism that enables organisms
to manifest appropriate seasonal responses. For example, we showed
that visible light and temperature regulate the splicing efficiency
of a clock mRNA, an event that sets the phase of when flies are
active during the day; e.g., at warm temperatures splicing efficiency
is low leading to an increase in nocturnal activity, hence minimizing
the deleterious affects associated with being active during the
hot mid-day sun. An overriding theme of the lab is that we try to
integrate molecular findings with real-life physiological relevance.
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| For complete list: PubMed
Majercak, J., Cheng, W.-F. and Edery, I.
(2004). Splicing of the period gene
3’-terminal intron is regulated by light, circadian clock
factors, and phospholipase C. Mol. Cell. Biol. 24: 3359-3372.
Akten, B., E. Jauch, G. K. Genova, E. Y.
Kim, I. Edery, T. Raabe, F. R. Jackson. (2003). A role
for CK2 in the Drosophila circadian oscillator. Nature Neurosci.
6: 251-257.
Kim, E.Y., Bae, K., Ng, F.S., Glossop,
N.R.J., Hardin, P.E. and Edery, I. (2002). Drosophila CLOCK
protein is under posttranscriptional control and influences light-induced
activity. Neuron 34:69-81.
Ko, W.H., Jiang, J. and Edery, I. (2002).
A role for Slimb in the degradation of Drosophila PERIOD protein
phosphorylated by DOUBLETIME Nature 420:673-678.
Bae, K.,
Lee, C., Hardin, P.H., and Edery, I. (2000) dCLOCK is present
in limiting amounts and likely mediates daily interactions between
the dCLOCK-CYC transcription factor and the PER-TIM complex. J.
Neuroscience 20: 1746-1753.
Edery, I.
(2000) Circadian rhythms in a nutshell. Physiol. Genomics
3: 59-74.
Majercak, J., Sidote, D., Hardin, P.H.
and Edery, I. (1999). How a circadian clock adapts to seasonal
decreases in temperature and day length. Neuron 24:219-230.
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