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The Mouse Sleep & Circadian Clinic Lausanne – University of Lausanne

The Mouse Sleep & Circadian Clinic Lausanne - University of Lausanne

Center for Integrative Genomics

The Mouse Sleep & Circadian Clinic Lausanne

Contact: Paul  
Franken
Position: M.E.R.-1 (Assistant Professor)
Address: Genopode building, 1015
City: Lausanne
Country: Switzerland
Phone: +41 21 692 3972
Contact Email: Contact laboratory
Website: http://www.unil.ch/cig/home.html
RESEARCH DOMAIN: Basic Animal
KEYWORDS: Genetics of Sleep, Pharmacology of Sleep, Sleep and Ageing, Sleep and Body Functions (Cardio-Respiratory, Thermoregulation/Metabolism, Endocrine), Sleep Physiology-Neurophysiology in Animal, Light and Non-Classical Photoreception, Biological Rhythms

CURRENT ANNOUNCEMENTS:

Laboratory Description:

We study the interaction between the two main processes that regulate sleep; i.e., homeostasis and circadian rhythms, at the behavioral, electrophysiological, molecular, and genetic levels. To gain inside into the molecular correlates of the homeostatic process and its interaction with the circadian process we combine forward, molecular, and reverse genetic approaches in the mouse. As a forward genetics approach we use QTL mapping in Recombinant Inbred strains and GWAS in outbred mice. To facilitate sleep phenotyping of large numbers of mice we helped develop and validate a novel non-invasive and high throughput method. For molecular genetic approaches we use transcriptome profiling of mRNA and micro-RNA transcripts in the brain under baseline and sleep deprivation conditions, in adrenalectomized mice, and after pharmacologically induced waking in various inbred strains of mice. Reverse genetic approaches are used in another line of research, which concerns our discovery that circadian clock genes not only keep track of time-of-day but also of time-spent-awake. We now investigate the mechanisms by which clock genes affect sleep homeostasis. The observation that the DNA binding of CLOCK, BMAL1, and NPAS2 both depends on intracellular energy charge and prior sleep-wake history is an exciting clue we are investigating using in vivo imaging techniques.

We use mathematical modeling approaches to quantify the complex non-linear relationship between changes in clock gene expression in the forebrain, sleep need, and the sleep-wake distribution.

KEY Publications of the Laboratory:

Franken, Dijk, Tobler, Borbély (1991) Sleep deprivation in rats: effects on EEG spectra, vigilance states, and cortical temperature, Am J Physiol 261: R198-208
Franken, Chollet, Tafti (2001) The homeostatic regulation of sleep need is under genetic control. J Neurosci 21: 2610-21
Ruby, Brennan, Xie, Cao, Franken, Heller, O’Hara (2002) The role of melanopsin in circadian responses to light. Science 298: 2211-3
Wisor, O’Hara, Terao, Selby, Kilduff, Sancar, Edgar, Franken (2002) A role for cryptochromes in sleep regulation. BMC Neurosci 3: 20
Dudley, Erbel-Sieler, Estill, Reick, Franken, Pitts, McKnight (2003) Altered Patterns of Sleep, Activity and Behavioral Adaptability in NPAS2-Deficient Mice. Science 301: 379-83
Tafti, Petit, Chollet, Neidhart, de Bilabao, Kiss, Wood, Franken (2003) Deficiency in short-chain fatty acid β-oxidation affects theta oscillations during sleep. Nature Genetics: 34: 320-5
Maret, Franken, Dauvilliers, Ghyselinck, Chambon, Tafti (2005) Retinoic acid signaling affects cortical synchrony during sleep. Science 310: 111-3
Franken, Dudley, Estill, Barakat, Thomason, O’Hara, McKnight (2006) The transcription factor NPAS2 affects the regulation and EEG of non-REM sleep: genotype and sex interactions. PNAS 103: 7118-23
Maret, Dorsaz, Gurcel, Pradervand, Petit, Pfister, Hagenbuchle, O’Hara, Franken, Tafti (2007) Homer1a is a core brain molecular correlate of sleep loss. PNAS 104: 20090-5
Cueni, Canepari, Emmenegger, Watanabe, Bond, Franken, Adelman, Lüthi (2008) T-type Ca2+ channels, SK2 channels and SERCAs gate sleep-related oscillations in thalamic dendrites. Nature Neurosci 11: 683-92
Andretic, Franken, Tafti (2008) Genetics of Sleep. Annu Rev of Genet 42: 361-88
Franken, Dijk (2009) Circadian clock genes and sleep homeostasis. Eur J Neurosci 29: 1820-9
Tsai, Hannibal, Hagiwara, Colas, Ruppert, Ruby, Heller, Bourgin*, Franken* (2009) Melanopsin as a sleep modulator: circadian gating of the direct effects of light on sleep and altered sleep homeostasis in Opn4−/− mice. PLoS Biol 7: e1000125
Mongrain, Hernandez, Pradervand, Dorsaz, Curie, Hagiawara, Gip, Heller, Franken (2010) Separating the contribution of glucocorticoids and wakefulness to the molecular and electrophysiological correlates of sleep homeostasis. Sleep 33: 1147-57
Curie, Mongrain, Dorsaz, Mang, Emmenegger, Franken (2012) Homeostatic and circadian contribution to EEG and molecular state variables of sleep regulation. Sleep (in press)

COLLABORATIONS:

  • Title:  PhD, MD Name:  Bo Gao Position: Research Associate Institution: Inselspital Bern Email: 
  • Title:  PhD Name:  Valérie Mongrain Position: Professor Institution: University of Montreal Email: 
  • Title:  PhD Name:  Bruce O'Hara Position: Professor Institution: University of Kentucky Email: 
  • Title:  PhD, MD Name:  Johan Auwerx Position: Profesor Institution: EPFL (ETH Lausanne) Email: 
  • Title:  PhD Name:  Ioannis Xenarios Position: Professor Institution: Swiss Institute of Bioinformatics Email: 
  • Title:  PhD Name:  Bernard Thorens Position: Professor Institution: University of Lausanne Email: 
  • Title:  PhD Name:  Anne Vassalli Position: Research Associate Institution: University of Lausanne Email: 
  • Title:  PhD, MD Name:  Jonathan Flint Position: Professor Institution: University of Oxford Email: 
  • Title:  PhD Name:  Patrice Bourgin Position: Professor Institution: University of Strasbourg Email: 
  • Title:  PhD Name:  Jérôme Nicod Position: Post-doctoral fellow Institution: University of Oxford Email: 
  • Title:  PhD Name:  Ueli Schibler Position: Professor Institution: University of Geneva Email: 
  • Title:  PhD Name:  Mehdi Tafti Position: Professor Institution: University of Lausanne Email: 
  • Title:  MD Name:  Adriano Fontana Position: Professor Institution: University of Zürich Email: 
  • Title:  PhD Name:  Urs Albrecht Position: Professor Institution: University of Fribourg Email: