History
In the past, our structure-function analyses of the circadian photoreceptor Drosophila cryptochrome (dCRY), the clock protein mouse cryptochrome1 (mCRY1) and the complex of mCRY1 with the clock protein PERIOD2 (mPER2) have provided important new insights into the phototransduction mechanism of dCRY as well as into the protein interactions and cellular functions of mammalian cryptochromes (Czarna et al, 2013, Schmalen et al, 2014). Likewise, our crystal structures and structure-based analyses of the PAS (PER-ARNT-SIM) domains of the Drosophila and mammalian PER proteins (dPER, mPER1,2,3) have shed light on the versatile functions of these interaction modules in the circadian clock and explained, for example, how a single point mutation in the dPER protein extends the fly's day to about 29 hours by affecting protein interactions (Yildiz et al, 2005; Hennig et al, 2009; Kucera et al, 2012). Furthermore, we have determined Cryo-EM structures of a Timeless (Tim)-Tipin-RPA complex, which plays a role in genome maintenance (Witosch et al, 2014) and of the moonlight sensitive cryptochrome L-Cry of Platynereis dumerilii (Vu et al, 2023) which is involved in the circalunar control of reproduction cycles (Poehn et al, 2022).
Current projects
We are following the line of investigating the complexity of Circalunar and Circadian Clocks by biochemical, biophysical and structural analyses of clock proteins. We apply a broad range of techniques, including cloning, mutagenesis, recombinant protein expression, chromatographic protein purification, (time-resolved) UV/VIS spectroscopy, the biochemical analyses of protein interactions (e.g. by SEC, native PAGE, pulldowns, MALS, EMSA), quantitative protein interaction studies (e.g. by fluorescence polarization, ITC), and structural analyses by X-ray crystallography and Cryo-EM.
Our main research aims are:
- The structural, biochemical and biophysical analysis of clock protein interactions, activities or conformational changes maintaining the 24 h transcription/translation feedback loop of the mammalian circadian oscillator.
- To provide molecular-mechanistic insights into the evolution of circadian clocks.
- To understand the molecular bases of circalunar timing (moonlight synchronization and circalunar oscillators) in marine organisms.
- To understand the connection of the mammalian circadian clock to genome maintenance.