D2: The circadian feedback module – assembly and localization as crucial events for circadian dynamics

Mammalian cells generate molecular ~24-hour rhythms using a multi-protein complex that eventually negatively regulates the expression of its components. Since the dynamics of this mechanism is poorly understood, we propose to study: (i) the role of transportin1-mediated nuclear transport using FRAP and interaction experiments; (ii) the role of  COPI vesicles for module assembly using FRET, co-immunoprecipitation and mass spectrometry; and (iii) the identity and dynamics of module composition using quantitative mass spectrometry and subsequent functional analyses.

Selected Publications

Azzi, A, Dallmann, R, Casserly, A, Rehrauer, H, Patrignani, A, Maier, B, Kramer, A, and Brown, SA
Circadian behavior is light-reprogrammed by plastic DNA methylation.
Nat Neurosci 2014; 17(3):377-382.
Schmalen, I, Reischl, S, Wallach, T, Klemz, R, Grudziecki, A, Prabu, JR, Benda, C, and Kra-mer, A. & Wolf, E
Interaction of circadian clock proteins CRY1 and PER2 is modulated by zinc binding and disul-fide bond formation.
Cell 2014; 157(5):1203-15.
Wallach T., Schellenberg K., Maier B., Kalathur R.K.R., Porras P., Wanker E.E., Futschik M.E. & Kramer A
Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions.
Plos Genet 2013; 9(3):e1003398.
Maier B. & Kramer A
A NONO-gate times the cell cycle.
P Natl Acad Sci USA 2013; 110(5):1565-6.
Granada A.E., Bordyugov G., Kramer A. & Herzel H
Human chronotypes from a theoretical perspective.
PLoS ONE 2013; 8(3):e59464.
Czarna A., Berndt A., Singh H.R., Grudziecki A., Ladurner A.G., Timinszky G., Kramer A. & Wolf E
Structures of Drosophila cryptochrome and mouse cryptochrome1 provide insight into circadian function.
Cell 2013; 153:1394-405.
Spörl F., Korge S., Jürchott K., Wunderskirchner M., Schellenberg K., Heins S., Specht A., Stoll C., Klemz R., Maier B., Wenck H., Schrader A., Kunz D., Blatt T. & Kramer A
Krüppel-like factor 9 is a circadian transcription factor in human epidermis that controls proliferation of keratinocytes.
P Natl Acad Sci USA 2012; 109(27):10903-8.
Kowalska E., Ripperger J.A., Muheim C., Maier B., Kurihara Y., Fox A.H., Kramer A. & Brown S.A
Distinct roles of DBHS family members in the circadian transcriptional feedback loop.
Mol Cell Biol 2012; 32(22):4585-94.
Kucera N, Schmalen I, Hennig S, Öllinger R, Strauss H, Grudziecki A, Wieczorek C, Kramer A, Wolf E
Unwinding the differences of the mammalian PERIOD clock proteins from crystal structure to cellular function.
Proc Natl Acad Sci USA 2012; 109:3311-3316.
Reischl, S, and Kramer A
Kinases and phosphatases in the mammalian circadian clock.
FEBS 2011; Lett 585:1393-1399.

Project Investigator

Prof. Dr. Achim Kramer

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