Keeping time: molecular entrainment mechanisms of biological clocks


The circadian system regulates processes from gene expression to behaviour in organisms from all phyla. When organisms are held in constant conditions, daily oscillations continue, often without dampening, and clock genes have been identified in several genetic model systems. In nature, the circadian clock functions predominantly in the entrained state, synchronized by environmental signals called zeitgebers. Furthermore, entrainment adapts according to conditions mimicking the changing seasons. Despite intensive research on circadian clock genes involved in circadian rhythms, the crucial players involved in circadian entrainment still have to be identified and studied. Central to this proposal is an analysis of entrainment at all levels of the system, as a key to understanding this fundamental biological programme.

This proposal describes projects that will harness two simple clock model systems, Neurospora crassa and Caenorhabditis elegans, to study circadian entrainment. Fundamental questions include which parts of the system determine entrained phase, how do they do it and what are the benefits of entrainment to the organism? Basic entrainment properties will be extensively characterized and used to structure a molecular description of entrainment. Reporter genes will be used to follow key components within multi-oscillator clock networks. Properties of entrainment will be probed to understand the dynamics of coupling between biological and physical oscillators, as well as of biological oscillators with each other. The work described here will set the stage for approaches in higher organisms, which are not as tractable due to their inherent complexity. The first publication concerning entrainment of oscillators (actually, pendulum clocks) was by the Dutch scientist, Christiaan Huygens, in the 17th century [1]. Here, we re-visit his observations with relevance to life in the 21st century.


Scientific article

  • T. Roenneberg, M.W. Merrow(2005): Demasking biological oscillators:"Prpoperties ans priciples of entrainment exemplified by the Neurospora circadian clock Proc. Natl. Acad. Sci. pp. 7742 - 7747
  • T. Roenneberg, M.W. Merrow(2005): Circadian Clocks: Translation Lost Current Biology pp. 470 - 473
  • M. Merrow, C. Boesl, T. Roenneberg(2005): Cellular clocks: circadian rhythms in primary human fibroblasts J. Biosci. pp. 101 - 103
  • M. Wittman, J. Dinnich, M. Merrow, T. Roenneberg(2006): Social jetlag: misalignment of biological and social time Chronobiology International pp. 71 - 80
  • M. Merrow, G. Mazzotta, Z. Chen, T. Roenneberg(2006): The right place at the right time: the regulation of daily timing by phosphorylation Genes and Development pp. 2629 - 2632
  • T. Roenneberg, T. Kuehnle, M. Juda, T. Kanterrmann, K. Allebrandt, M. Gordijn, M. Merrow(2007): Epidemiology of the human circadian clock Sleep Med. Rev. pp. 429 - 438
  • T. Kantermann, M. Juda, M. Merrow, T. Roenneberg(2007): The human circadian clock's seasonal adjustment is disrupted by daylight saving time Current Biology pp. 1996 - 2000
  • M. Merrow, T. Roenneberg(2007): Circadian clock: Time for a phase shift of ideas? Current Biology pp. R636 - 638
  • K. Sveric, M. Mason, T. Roenneberg, M. Merrow(2007): Novel strategies for identification of clock genes in Neurospora using isertional mutagenesis Methods Mol. Biol. pp. 173 - 185
  • T. Roenneberg, C.J. Kumar, M. Merrow(2007): The circadian clock of homo sapiends entrains to sun time Current Biology pp. R44 - R45
  • M. Brunner, M.W. Merrow(2008): Lego Clocks: building a clock from parts. Genes and development pp. 1422 - 1426
  • M. Brunner, M.W. Merrow(2008): The green yeast uses its plant-like clock to regulate its animal-like tail Genes and development pp. 825 - 831
  • M.W. Merrow, M.F.P.M. Maas(2009): Circadian clocks: evolution in the shadows Curr. Biol. pp. R1042 - 5
  • M.W. Merrow, et al(2010): A chronobiologist makes sense of circadian dysfunction in illness. Nature pp. 135
  • M.W. Merrow, et al(2010): Modeling a circardian surface. J. Biol. Psych. pp. 340 - 9
  • M.W. Merrow, et al(2010): Clock gene variants associate with sleep duration in two independent populations J. Biol. Psych.
  • M.W. Merrow, et al(2010): Genetic and molecular characterization of a cryptochrome from the filamentous fungus Neurospora crassa Eukaryot, Cell pp. 738 - 50
  • M.W. Merrow, et al(2010): A circardian surface of entrainment: varying T, t and photoperiod in Neurospora crassa. J. Biol Psych. pp. 318 - 328
  • M.W. Merrow, et al(2010): Entrainment concepts revisited. J.Biol Psych. pp. 329 - 39
  • M.W. Merrow, et al(2011): Perfect timing: epigenetic regulation of the circardian clock. FEBS Lett. pp. 1406 - 11
  • M.W. Merrow, et al(2012): Circardian regulation of olfaction and an evolutionarily conserved, nontranscriptional marker in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America pp. 20479 - 20484
  • M.W. Merrow, et al(2012): Peroxiredoxins are conserved markers of circardian rhythms. Nature pp. 459 - 64
  • M.W. Merrow, et al(2012): Social jetlag and obesity. Curr. Biol. pp. 939 - 43

Publications for the general public

  • (2007): Participation in Bessensap 2007


Project number


Main applicant

Prof. dr. M.W. Merrow

Affiliated with

Ludwig-Maximilians-Universit√§t M√ľnchen, Institute of Medical Psychology

Team members

Drs. J. Bosman, Drs. E. Eelderink, Dr. F.C. Gomes, Prof. dr. R.A. Hut, Dr. ir. M.F.P.M. Maas, Prof. dr. M.W. Merrow, Dr. M. Olmedo, Drs. M.M.T. van der Pol, Drs. M. Raven, Dr. T. van Wessel


01/02/2006 to 07/02/2014