Novel clock genes and principles
Sub-Project 4: Novel clock genes and principles
About 10 clock genes, orthologous in sequence but not necessarily analogous in function, are
known in mammals and Drosophila but numerous results indicate many remain to be identified.
A QTL study indicates 14 as-yet-unidentified loci that regulate period
or phase in mice. Mutant screens have generated mice that carry
mutations at heretofore un-described loci. Crosses of individuals with
similar clock properties have a wide distribution of clock properties
(i.e., period,
phase) suggesting extremely complex genetic regulation. The most
extreme phase mutant among the collection of clock mutant animals is
the tau mutant hamster. The mutation is in a casein kinase encoding
gene that modifies the core molecular feedback loop but is not itself a
transcription factor. The identification of new clock genes has been
one of the main driving forces in the field. Each new gene adds to our
insight into pathways and networks with clock mechanisms involved. This
Sub-Project proposes to identify novel clock genes and polymorphisms or
clock principles in humans, mice and Drosophila. This cross-species
approach allows us to capitalize on the advantages of detection of
variant genes in different organisms. At the same time it prepares the
ground for functional experiments in these model organisms.
Sub-Project Leader: Prof. Martha Merrow, PhD, University of Groningen, Chronobiology
Members:
Publications
2006
Carpen, J. D., M. von Schantz, et al. (2006). "A silent polymorphism in the PER1 gene associates with extreme diurnal preference in humans." J. Hum. Genet. 51: 1122-1125.
Wittmann, M., J. Dinich, et al. (2006). "Social jet-lag: sleep, well-being and stimulus consumption of different chronotypes." Chronobiol. Int. 23(1&2): 497-509.
Roenneberg, T., C. J. Kumar, et al. (2007). "The human circadian clock entrains to sun time." Curr. Biol. 17: R44-R45.
Vanselow K, Vanselow JT, Westermark PO, Reischl S, Maier B, Korte T, Herrmann A, Herzel H, Schlosser A, Kramer A. Differential effects of PER2 phosphorylation: molecular basis for the human familial advanced sleep phase syndrome (FASPS). Genes Dev. 2006 Oct 1;20(19):2660-72. Epub 2006 Sep 18.
2007
Allebrandt, K.V. & Roenneberg, T. (2007) The Search for circadian clock components in humans: new perspectives for association studies. Brazilian J Med Bio Research; submitted
Glaser F. and Stanewsky R (2008) Synchronization of the Drosophila circadian clock by temperature cycles (in press: Cold Spring Harbor Symposium on Quantitative Biology)
Merrow M and Roenneberg T (2007) Circadian clock: time for a phase shift of ideas? Curr Biol 17:R636-638.
Merrow M. and Roenneberg T. (in press) Circadian entrainment of Neurospora crassa. Cold Spring Harbor Proceedings.
Roenneberg, T.; Kuehnle, T.; Juda, M.; Kantermann, T.; Allebrandt, K.; Gordijn, M.; Merrow, M. (2007) Epidemiology of the human circadian clock. Sleep Med Rev 11:429-38.
Roenneberg T. and Merrow M. (in press) Entrainment of the human circadian clock. Cold Spring Harbor Proceedings.
Sandrelli F., Tauber E., Pegoraro M., Mazzotta G., Cisotto P., Landskron J., Stanewsky R., Piccin A., Rosato E., Zordan M., Costa R., and Kyriacou C.P. (2007). A molecular basis for natural selection at the timeless locus in Drosophila melanogaster. Science 316: 1898-1900.
Stanewsky R (2007) Analysis of rhythmic gene expression in adult Drosophila using the firefly luciferase reporter gene. Methods Mol Biol 362: 131-42.
Sveric K, Mason M, Roenneberg T and Merrow M (2007) Novel strategies for identification of clock genes in Neurospora with insertional mutagenesis. Methods in molecular biology (Clifton, NJ 362:173-185.
Veleri S., Rieger D., Helfrich-Förster C., and Stanewsky R. (2007). Hofbauer-Buchner eyelet affects circadian photosensitivity and coordinates TIM and PER expression in Drosophila clock neurons. J Biol Rhythms 22: 29-42.
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