Circadian control of WCC by phosphatase-resistant phosphoclusters

• Applicant: Professor Dr. Michael Brunner
• Subject Area: Biochemistry
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 560571244

Circadian clocks are cell-based molecular oscillators that generate self-sustaining rhythms with a period in the range of 24 hours. Recurring stimuli related to the geophysical cycle of the Earth's rotation, such as light and temperature, synchronize the circadian clock with the external day-night cycle. This synchronization creates an internal reference phase that allows organisms to anticipate the daily recurring environmental changes. In this proposal, we will investigate the molecular mechanisms that determine the phase of the circadian clock of Neurospora crassa. Our preliminary data suggest that redundant multisite phosphorylation of the circadian transcription factor WCC generates inhibitory phospho-clusters that are quite resistant to phosphatases. Resistance to dephosphorylation provides the mechanistic basis for the time-delayed reactivation of WCC and thus determines the correct circadian phase. We will investigate the mechanisms underlying the formation of thermodynamically persistent phospho-clusters and how these clusters influence the activity of WCC. Our preliminary results suggest that our findings are of general relevance for the understanding of protein regulation by multisite phosphorylation.

• DFG Programme: Research Grants