Thanks to genetic and biochemical advances on the molecular mechanism of ci
rcadian rhythms in Drosophila, theoretical models closely related to experi
mental observations can be considered for the regulatory mechanism of the c
ircadian clock in this organism. Modeling is based on the autoregulatory ne
gative feedback exerted by a complex between PER and TIM proteins on the ex
pression of per and tim genes. The model predicts the occurrence of sustain
ed circadian oscillations in continuous darkness. When incorporating light-
induced TIM degradation, the model accounts for damping of oscillations in
constant light, entrainment of the rhythm by light-dark cycles of varying p
eriod or photoperiod, and phase shifting by light pulses. The model further
provides a molecular dynamical explanation for the permanent or transient
suppression of circadian rhythmicity triggered in a variety of organisms by
a critical pulse of light. Finally, the model shows that to produce a robu
st rhythm the various clock genes must be expressed at the appropriate leve
ls since sustained oscillations only occur in a precise range of parameter
values. (C) 2000 John Wiley & Sons, Inc.