Mehdi Tafti Laboratory

Presentation

Sleep, Associated functions, and Sleep Disorders

Sleep occupies one third of our life but we ignore largely its functions. Sleep not only regulates our vigilance but interacts with the whole physiology, including but not limited to neuroendocrine, metabolic, cardiovascular and neurocognitive systems. In our laboratory, we investigate the basic molecular and cellular mechanisms controlling sleep and associated functions. We are also interested in understanding the cause of several sleep disorders, including narcolepsy, parasomnias and sleep apnea.

Representative publications:

Liblau RS, Vassalli A, Seifinejad A, Tafti M. Hypocretin (orexin) biology and the pathophysiology of narcolepsy with cataplexy. Lancet Neurol. 2015, 14:318-28.

Vassalli A, Dellepiane JM, Emmenegger Y, Jimenez S, Vandi S, Plazzi G, Franken P, Tafti M. Electroencephalogram paroxysmal θ characterizes cataplexy in mice and children. Brain. 2013, 136:1592-608.

Hinard V, Mikhail C, Pradervand S, Curie T, Houtkooper RH, Auwerx J, Franken P, Tafti M. Key electrophysiological, molecular, and metabolic signatures of sleep and wakefulness revealed in primary cortical cultures. J Neurosci. 2012, 32:12506-17.

Hor H, Kutalik Z, Dauvilliers Y, Valsesia A, Lammers GJ, Donjacour CE, Iranzo A, Santamaria J, Peraita Adrados R, Vicario JL, Overeem S, Arnulf I, Theodorou I, Jennum P, Knudsen S, Bassetti C, Mathis J, Lecendreux M, Mayer G, Geisler P, Beneto A, Petit B, Pfister C, Burki JV, Didelot G, Billiard M, Ercilla G, Verduijn W, Claas FH, Vollenweider P, Waeber G, Waterworth DM, Mooser V, Heinzer R, Beckmann JS, Bergmann S, Tafti M. Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy. Nat Genet. 2010, 42:786-9.

Cvetkovic-Lopes V, Bayer L, Dorsaz S, Maret S, Pradervand S, Dauvilliers Y, Lecendreux M, Lammers GJ, Donjacour CE, Du Pasquier RA, Pfister C, Petit B, Hor H, Muhlethaler M, Tafti M. Elevated Tribbles homolog 2-specific antibody levels in narcolepsy patients. J Clin Invest. 2010, 120:713-719.

Maret S, Dorsaz S, Gurcel L, Pradervand S, Petit B, Pfister C, Hagenbuchle O, O'Hara BF, Franken P, Tafti M. Homer1a is a core brain molecular correlate of sleep loss. Proc Natl Acad Sci U S A. 2007, 104:20090-20095.

Maret S, Franken P, Dauvilliers Y, Ghyselinck NB, Chambon P, Tafti M. Retinoic acid signaling affects cortical synchrony during sleep. Science. 2005, 310:111-113.

Tafti M, Petit B, Chollet D, Neidhart E, de Bilbao F, Kiss JZ, Wood PA, and Franken P. Deficiency in short-chain fatty acid b-oxidation affects theta oscillations during sleep. Nat. Genet., 2003, 34: 320-325.

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Research

Basic Genetic and Metabolic Aspects of Sleep

Based on available literature there is no doubt that many aspects of sleep are under a genetic control in both humans and animal models. These include not only the amount and the distribution of sleep but also very specific electroencephalographic (EEG) features of sleep and wakefulness. By using the inbred mouse as a genetic tool, we have been able to demonstrate that sleep as a quantitative trait is amenable to quantitative trait loci analysis (QTL). We have been the first to report that a single gene dramatically affects the quantitative sleep EEG. An EEG variant specific to paradoxical sleep (slow theta frequency) has been identified as the most heritable phenotype in inbred mice and subsequent mapping and functional studies identified a metabolic enzyme Acads (acyl Coenzyme A dehydrogenase for short chain fatty acids) as the underlying gene. More recently, we have shown that the slow wave activity during sleep is also affected by a single gene (Rarb) involved in the vitamin A signaling pathway. We are now concentrating our research efforts on the genetic dissection of sleep need. Sleep need is homeostatically regulated (loss of sleep leads to compensatory processes, which are responsible for deeper recovery sleep). A gene for sleep need has been mapped on the mouse chromosome 13. Gene expression profiling after sleep deprivation to investigate the molecular correlates of prolonged wakefulness, identified Homer1a on chromosome 13 as the best molecular marker of sleep need. Finally, we have established an in vitro model of sleep (sleep in a dish), which presents the electrophysiological, transcriptome and metabolome correlates of sleep and wakefulness in intact animals. By using this model, we have shown that extended wakefulness or sustained stimulation of cortical cultures lead to compromised membrane metabolism.

Genetics of sleep disorders

Many sleep disorders run in families but their genetic bases are poorly understood. Our laboratory is specialized in the genetics of narcolepsy and sleepwalking. We perform family – and population – based studies using linkage, candidate gene, and genome-wide associations. We have also initiated a Center for Investigation and Research in Sleep (CIRS) in collaboration with the Department of Medicine of the University Hospital (CHUV), Lausanne, where we conduct sleep research in normal subjects and patients with sleep disorders. We have localized the first familial susceptibility gene for narcolepsy and have reported the first genetic evidence in sleepwalking. Future plans include genetics of normal sleep in twins, families, and the general population.

Members

Professor Mehdi Tafti, group leader

Mehdi Tafti received his PhD from the University of Montpellier (France) in 1991 after completing his doctoral thesis on sleep regulation in human narcolepsy. He performed a postdoctoral fellowship with Dr. Mignot and Dr. Dement and was a Research Associate at the Department of Psychiatry and Biological Sciences at Stanford University. In 1995 he moved to the Department of Psychiatry in Geneva where he established the first laboratory dedicated to the molecular genetics of sleep and sleep disorders. He joined the Center for Integrative Genomics, University of Lausanne in 2004 and co-founded the Center for Investigation and Research in Sleep at CHUV, Lausanne. He is now Professor at the Department of Physiology, University of Lausanne.

Corinne Pfister, Lab technician

Corinne obtained her MS in Microbiology from the University of Lausanne. She then joined the group of Prof. Bernard Rossier at the Department of Pharmacology and Toxicology at UNIL as a lab technician. In 2004 she joined the Mehdi Tafti’s lab at the Center for Integrative Genomics.

Ali Seifinejad, Chercheur FNS senior

Ali received his master of science in agricultural Biotechnology from university of Tehran and after that worked for about five years in Royan institute in Tehran establishing human iPS cell lines. In 2012 he joined Tafti lab to do his PhD and he graduated in 2016. After his PhD, he is still in Tafti lab as Post-doctoral and senior scientist. Since the time he joined Tafti lab, he has been working on molecular, cellular and behavioral aspects of sleep and sleep disorders.

Dr. Anne Vassalli, Senior Research Associate

Anne did her PhD thesis at MIT with Prof Rudolf Jaenisch, and then a postdoc at the Rockefeller University in New York on molecular genetics of olfaction in mice. She joined the TAFTI lab in 2007 to switch to the sleep field and behavioral state regulation, where she developed mouse models to study narcolepsy and hypocretin/orexin signaling circuits.

Gianandrea Broglia, PhD student

A background in psychology with a Bachelor obtained from University of Milano-Bicocca and a successive MSc in neuroscience at University College London, brought Gianandrea in 2014 to work at the University of Copenhagen in Prof. Roland group. In Denmark he performed in vivo cortical recordings of rodent primary visual areas. Consecutively in 2016, at the Italian Institute of Technology in Genova, he explored circadian genes expression and synchronization on in vitro neurons and astrocytes cultures hosted by the Dr. De Pietri Tonelli lab.
He joined Prof. Tafti group at UNIL in early 2019 to start his PhD concerning sleep and brain rhythms.

Marie-Laure Possovre, PhD student

Marie-Laure did her Bachelor in Nancy (France). She obtained a degree in Biology, with a specialization in Neurosciences, Immunology and Physiology. During this Bachelor she make a Trainingship in the Laboratory INSERM U954 (Nancy, France) working on: «study the consequences of a methyl donor deficiency on the developing central nervous system » under the direction of Prof. Dr. Carine BOSSENMEYER POURIE. She did her French/German Master of cellular and integrative Neurosciences at the University of Strasbourg and the University of Saarland (Saarbrücken, Germany). During this Master she was intern in the Laboratory of Neurosciences (INSERM 118, Strasbourg) and had working about "Central and peripheral mechanism of neurodegeneration" with Dr ROUAUX Caroline. She did her Master thesis in the laboratory "Zentrum für Human-und Molekularbiologie" (Saarbrücken) directed by Prof. Dr. Uli Müller.

Dr. Mojtaba Bandarabadi, postdoctoral fellow

Mojtaba received his PhD from the University of Coimbra (Portugal) in 2015, with focus on modelling the neurophysiological dynamics of epileptic brain during preictal and ictal events. During his PhD, he was a visiting scholar at the University of Minnesota (USA) for 6 months. He did a postdoc at the Department of Neurology, the Hospital University of Bern, and developed expertise and interests in system neuroscience focusing on the neural circuits and dynamics of sleep-wake cycle. Mojtaba joined Tafti’s group in February 2018 to pursue his research interests in the sleep field, and is currently working on the neural substrates of sleep-wake cycles and oscillations.

Dr. Sha Li, Postdoctoral fellow

After her Diploma of Medicine obtained in 2005 at the Kunming Medical College in China, she obtained a Master of Physiology from Sun Yat-Sen University, Guangzhou, China in 2008. And then she pursued her studies during 2008-2009 at the University Claude Bernard in Lyon, France, working on sleep/wake regulation, then moved to the lab of Prof. Haas at Heinrich-Heine University in Düsseldorf, Germany. In 2015, she accomplished her Phd under supervison of Prof. Mehdi Tafti and Dr Anne Vassalli. From February 2017, she joins the same lab as post-doc.