Research interests

Many organisms have evolved circadian clocks to anticipate environmental changes associated with the 24h night-day cycle of earth rotation. Circadian clocks are time-keeping devices that organize daily expression profiles of a large number of genes (~10% in eukaryotic organisms) and thus generate the potential to control thousands of biochemical, physiological and behavioral functions in a time-of-day specific manner. Circadian clocks are cell-autonomous oscillators composed of a network of interconnected positive and negative feedback loops that produce rhythmic expression and modification of one or more clock proteins. Circadian oscillations are self-sustained and persist without environmental cues with a ca. 24 h period. In nature, environmental signals, so-called zeitgebers such as light and temperature, are transduced to the clock to synchronize it with the 24 h period of earth rotation. The transcriptional activator WHITE COLLAR COMPLEX (WCC) is the central element of the circadian clock of Neurospora. Activity and abundance of the WCC are regulated in circadian fashion by the clock protein FREQUENCY (FRQ). FRQ, which is expressed under control of the WCC, inhibits it's the WCC in a negative feedback loop by promoting its phosphorylation and it supports accumulation of WCC in a positive loop. These conflicting functions of FRQ are coordinated in a temporal and spatial fashion. Assembly of clock protein complexes, their posttranslational modification, nuclear-cytoplasmic shuttling and regulated degradation are key steps in timekeeping on the molecular level. The molecular mechanisms underlying positive and negative feedback are in the main focus of our research.