PhD Position: Molecular interactions in the mammalian circadian clock (m/f/d)

The research group of Eva Wolf offers the following PhD project:
Many physiological processes are regulated in a day-time dependent (circadian) manner. In the primary gene regulatory feedback loop of the mammalian circadian clock, the transcription factors CLOCK and BMAL1 activate the expression of PERIOD (PER1,2,3) and Cryptochrome (CRY1,2) clock proteins, which feedback-repress CLOCK/BMAL1. Within a 24h day, CLOCK/BMAL1 cycles between an active state recruiting co-activators like MLL1, an early repressed state including CRY1/2, PER, CK1 kinase and other proteins, and a late repressed state where only CRY1 remains associated with CLOCK/BMAL1. Additionally, cytosolic CRY/PER/CK1 containing complexes are formed before the proteins enter the nucleus in a time-regulated manner. In a secondary feedback loop, the circadian expression of Bmal1 is regulated by the nuclear receptors REV-ERB and ROR.

PhD project: 3D structural and molecular mechanistic analyses of PERIOD protein interactions in the mammalian circadian clock

This PhD project aims to characterize the protein interactions of PERIOD clock proteins in the context of PER/CRY/CK1 containing complexes, employing in vitro protein biochemistry, high resolution 3D structure determination by X-ray crystallography or Cryo-EM, quantitative/biophysical protein interaction studies, spectroscopy and molecular biology. We recently showed that WDR5, a component of the CLOCK/BMAL1 co-activating MLL1 histone-methyltransferase complex, also forms a PER1/WDR5 complex, that affects circadian oscillations and is targeted by WDR5 WIN site inhibitors. In this PhD project the interactions between PER1, WDR5 and REV-ERB/ROR nuclear receptors will be further investigated on a molecular mechanistic and 3D structural level to understand how the PER1/WDR5 complex impacts the primary and secondary feedback loop of the mammalian circadian clock. The PhD candidate will also investigate the interaction interplay of PERIOD proteins with other protein components of CRY/PER/CK1 containing complexes.
We are looking for a highly motivated PhD candidate with significant previous exposure to theoretical and practical aspects of 3D-structural-, biochemical- and biophysical analyses of proteins and protein complexes during their bachelor/master education and practical experience in relevant techniques.

If you are interested in this project, please select Wolf as your group preference in the IPP application platform.

Are you an ambitious scientist looking to push the boundaries of research while interacting with colleagues from multiple disciplines and cultures? Then joining the IPP is your opportunity to give your scientific career a flying start!
All you need is:

• Master or equivalent
• Interactive personality & good command of English
• 2 letters of reference