Circadian System Biology

Most organisms show daily rhythms in physiology and behaviour synchronized with the environmental light/dark cycle. From cyanobacteria to humans, these rhythms are driven by self-sustained endogenous clocks oscillating with a circadian (~ 24 h) period. In mammals, circadian clocks are present in virtually all cells and are organized in a hierarchical and highly integrated system. The top of the mammalian circadian system is composed of a master clock located in the suprachiasmatic nuclei (SCN) of the hypothalamus which is reset everyday by the photic input from the retina and in turn coordinates the phase of local clocks outside the SCN and in the periphery in order to ensure optimal timing of the physiology. At the molecular level, central and peripheral clocks use a common set of clock genes which interact together to form a complex network of transcriptional/translational regulatory loops generating circadian oscillations in electrical activity, cellular metabolism, and transcription of clock-controlled genes. Functional genomics have established that circadian clocks regulate a significant proportion of the genome, with for instance an estimate of approximately 3000 genes being rhythmically expressed in the liver. Importantly, the clock regulated transcriptional programme is highly tissue-specific and nearly all key biological processes appear to be linked to the circadian clock system. Examples include, sleep/wake cycle, body temperature, hormone secretion, metabolism, blood pressure, cell division, and immune function. As a consequence, circadian disruption becomes increasingly recognized as an important factor in the context of major diseases such as cancer, metabolic syndrome, inflammation, sleep and depressive disorders.

Our long term objective is to understand how mammalian circadian clocks regulate physiological outputs and reciprocally, determine the mechanisms whereby key biological process influence circadian clock function. One of our current projects investigates the interactions between core clock genes and energy metabolism with a focus on the role of specific transcriptional regulators. A second line of research is dedicated to the identification and analysis of the molecular mechanism that integrate the circadian clock and cell cycle mechanisms in normal and cancer cells.


Simplified model of the molecular circadian clock in mammals


Basic organisation of the mammalian circadian system

 

Last publications

Sexual Dimorphism in Circadian Physiology Is Altered in LXRα Deficient Mice. - 2016 - PloS one - 11 Pe0150665 - Feillet C, Guérin S, Lonchampt M, Dacquet C, Gustafsson JÃ…, Delaunay F, and Teboul,M

A hybrid model of cell cycle in mammals. - 2016 - Journal of bioinformatics and computational biology - 14 P1640001 - Behaegel J, Comet JP, Bernot G, Cornillon E, and Delaunay,F

Coupling between the Circadian Clock and Cell Cycle Oscillators: Implication for Healthy Cells and Malignant Growth. - 2015 - Frontiers in neurology - 6 P96 - Feillet C, van der Horst GT, Levi F, Rand DA, and Delaunay,F

The hepatic circadian clock regulates the choline kinase α gene through the BMAL1-REV-ERBα axis. - 2015 - Chronobiology international - 32 P774-84 - Gréchez-Cassiau A, Feillet C, Guérin S, and Delaunay,F

Functional genomics identify Birc5/survivin as a candidate gene involved in the chronotoxicity of cyclin-dependent kinase inhibitors. - 2014 - Cell cycle (Georgetown, Tex.) - 13 P984-91 - Siffroi-Fernandez S, Dulong S, Li XM, Filipski E, Gréchez-Cassiau A, Peteri-Brì¼nback B, Meijer L, Lévi F, Teboul M, and Delaunay,F

Phase locking and multiple oscillating attractors for the coupled mammalian clock and cell cycle. - 2014 - Proceedings of the National Academy of Sciences of the United States of America - 111 P9828-33 - Feillet C, Krusche P, Tamanini F, Janssens RC, Downey MJ, Martin P, Teboul M, Saito S, Lévi FA, Bretschneider T, van der Horst GT, Delaunay F, and Rand,DA

Age-structured cell population model to study the influence of growth factors on cell cycle dynamics. - 2013 - Mathematical biosciences and engineering : MBE - 10 P1-17 - Billy F, Clairambault J, Delaunay F, Feillet C, and Robert,N

Impact of REV-ERB alpha gene polymorphisms on obesity phenotypes in adult and adolescent samples. - 2013 - International journal of obesity (2005) - 37 P666-72 - Goumidi L, Grechez A, Dumont J, Cottel D, Kafatos A, Moreno LA, Molnar D, Moschonis G, Gottrand F, Huybrechts I, Dallongeville J, Amouyel P, Delaunay F, and Meirhaeghe,A

A circadian clock transcription model for the personalization of cancer chronotherapy. - 2013 - Cancer research - 73 P7176-88 - Li XM, Mohammad-Djafari A, Dumitru M, Dulong S, Filipski E, Siffroi-Fernandez S, Mteyrek A, Scaglione F, Guettier C, Delaunay F, and Lévi,F

DNA microarray analysis and functional profile of pituitary transcriptome under core-clock protein BMAL1 control. - 2012 - Chronobiology international - 29 P103-30 - Guillaumond F, Becquet D, Boyer B, Bosler O, Delaunay F, Franc JL, and François-Bellan,AM

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Delaunay Franck
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2001 ACI Jeune chercheur

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Members Team
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   Grechez-Cassiau Aline
   Teboul Michèle
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   Behaegel Jonathan
   Leclere Pierre
   Ruberto Anthony
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   Tassone John
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