We are what we repeatedly do. Excellence, then, is not an act, but a habit. Aristotle
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
- Prof. Dr. Till Roenneberg, LMU Munich, Institute for Medical Psychology
- Prof. Dr. Ralf Stanewsky, Queen Mary &Westfield College, School of Biological Sciences
- Prof. Dr. Achim Kramer (Deputy Leader), Charit?, Achim Kramer Lab
- Prof. Dr. Thomas Meitinger, GSF, Institute of Human Genetics
- Prof. Dr. Andres Metspalu, Estonia Biocentre, Department of Biotechnology
- Prof. Dr. Andrew Millar, University of Edinburgh, Institute of Molecular Plant Science
- Prof. Dr. Ference Nagy, Biological Research Center, Institute of Plant Biology
- Prof. Dr. Pat Nolan, Medical Research Council, Medical Research Council
- Dr. François Rouyer, CNRS, Institute de Neurobiologie Alfred Fessard
- Dr. Konstantin Danilenko, Russian Academy of Medical Science, Institute of Internal Medicine
- Dr. Emma Perfect, LUX Biotechnology
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.
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.