The Clock in eukaryotic Cells
Project leader: Tanja Schwarzmeier, cand. med.
The circadian clock represents a fundamental aspect of biology that is possibly common to all cells. The clock imposes a temporal structure on processes from gene expression to behavior. Clocks are virtually always found in the entrained state in nature. Entrainment is the process whereby the circadian machinery is stably synchronized to the 24h environmental cycle. Entraining stimuli (zeitgebers) include light and numerous other reliable and predictable features of the environment stemming from the light cycle (e.g. temperature, food, etc.). Due to genetic and environmental variability (e.g. season), a distribution of entrained phases or chronotypes is observed in a given population. Thus, entrainment is not a single entity but rather a dynamic process and until we have figured out the rules therein we cannot understand daily timing.
We aim to elucidate the rules of entrainment using a novel approach, namely by describing and probing intracellular molecular oscillators. The clock in the organism is an amalgam of so-called peripheral clocks, such as liver, eye, kidney and heart. The human circadian clock is a combination of these organ oscillators, as they synchronize with the clock in the brain. However, each of these peripheral clocks is built from individual cells and thus it is the clock characteristics of cells that ultimately determine clock characteristics of the organism. How do they entrain? How do they respond to zeitgebers? What to their PRCs look like? What happens when two zeitgebers get involved? For this work, we exploit the simplest cellular clock systems for this work, from human tissue culture cells to S. cerevisiae.
Publications on this topic
A functional context for heterogeneity of the circadian clock in cells.
Merrow M, Harrington M.PLoS Biol. 2020 Oct 14;18(10):e3000927. doi: 10.1371/journal.pbio.3000927. eCollection 2020 Oct.PMID: 33052900
Insulin-like growth factor-1 acts as a zeitgeber on hypothalamic circadian clock gene expression via glycogen synthase kinase-3beta signaling.
Breit A, Miek L, Schredelseker J, Geibel M, Merrow M, Gudermann T.J Biol Chem. 2018 Nov 2;293(44):17278-17290. doi: 10.1074/jbc.RA118.004429. Epub 2018 Sep 14.PMID: 30217816
Sleeping Beauty? Developmental Timing, Sleep, and the Circadian Clock in Caenorhabditis elegans.
Olmedo M, Merrow M, Geibel M.Adv Genet. 2017;97:43-80. doi: 10.1016/bs.adgen.2017.05.001. Epub 2017 Jun 16.PMID: 28838356
The Circadian Clock and Human Health.
Roenneberg T, Merrow M.Curr Biol. 2016 May 23;26(10):R432-43. doi: 10.1016/j.cub.2016.04.011.PMID: 27218855
From behavior to mechanisms: an integrative approach to the manipulation by a parasitic fungus (Ophiocordyceps unilateralis s.l.) of its host ants (Camponotus spp.).
de Bekker C, Merrow M, Hughes DP.Integr Comp Biol. 2014 Jul;54(2):166-76. doi: 10.1093/icb/icu063. Epub 2014 Jun 6.PMID: 24907198
Circadian regulation of olfaction and an evolutionarily conserved, nontranscriptional marker in Caenorhabditis elegans.
Olmedo M, O'Neill JS, Edgar RS, Valekunja UK, Reddy AB, Merrow M.Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20479-84. doi: 10.1073/pnas.1211705109. Epub 2012 Nov 26.PMID: 23185015
A circadian clock in Saccharomyces cerevisiae.
Eelderink-Chen Z, Mazzotta G, Sturre M, Bosman J, Roenneberg T, Merrow M.Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2043-7. doi: 10.1073/pnas.0907902107. Epub 2010 Jan 19.PMID: 20133849