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.
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.
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.
Mehdi Tafti, Full Professor
|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.|
Anne Vassalli, Research Manager
|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.|
Mojtaba Bandarabadi, Postdoc
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.
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.
Cathy Gouelle, PhD student
I come from University of Rouen (in France) where I do my master degree in Neuroscience but I just began my experimental work in the laboratory of Pr. Pellerin. I had already the occasion to do an internship in this team during the summer 2015 as part of my bachelor degree and of the SUR (Summer Undergraduate Research) program of the University of Lausanne. During this internship I had started to study the role of lactate on the regulation of reproductive function. Then I completed my pre-master in 2016 for two months in team 2 of the INSERM U982 directed by Dr. David Vaudry and more specifically under the direction of Dr. Julien Chuquet with whom I worked on the role of ODN in post-ischemic synaptic plasticity. More particularly interested in energy homeostasis and its impact on the large physiological functions controlled by the hypothalamus, I decided to join again the team of Pr. Pellerin to continue the project on which I had worked one and a half year ago but now in the context of my master degree.
Meriem Haddar, Postdoc
Meriem obtained her Pharmacy degree (Pharm.D) in Ferhat Abbas University, Setif, in Algeria (2013). Then she worked for a pharmaceutical company for more than a year (Novapharm Trading). Later, she obtained the Japanese MEXT scholarship and moved to Japan for PhD studies in pharmacy (2015 to 2019). She joined the laboratory of Pharmaceutical Therapy and Neuropharmacology in the University of Toyama under the supervision of Prof. Atsumi Nitta. During her PhD, Meriem worked on methamphetamine addiction and cognitive function in mice. After graduation, Meriem stayed in the same lab as a foreign researcher until July 2020.
Anna Hadjichambi, Postdoc
|Anna Hadjichambi obtained her Bachelor degree in Biochemistry from the University of Warwick in the UK. Her final year project was focused on the fabrication and characterisation of biosensors for adenine. She then completed her Masters Degree in Neuroscience at UCL, where she worked with Prof. Gourine and Dr. Ackland on the real time measurement of glutamate release from phagocytes. Anna has completed her PhD in UCL, funded by the Grand Challenges UCL, which was a collaboration between the departments of Liver and Digestive health (Prof. Jalan) and Neuroscience, Physiology and Pharmacology (Prof. Gourine). Her thesis was entitled “The Neurochemistry of Hepatic Encephalopathy" and involvedexperimental studies conducted in animal (rat) models of hepatic encephalopathy, in vivoand in vitro, in combination with pharmacological approaches. The results obtained during her PhD provided the first evidence of a critical pathophysiologicalrole of ammonia in inducing neuronal energy deficit in hepatic encephalopathy due to impaired cerebraloxygenation, compromised hemichannel-mediated lactate transport betweenastrocytes and neurons and affected glymphatic clearance. In 2018 she joined the group of Prof. Pellerin, as a postdoctoral fellow, focusing her research on the role of cerebral lactate metabolism and transport (MCTs) on the development of cognitive deficits during non-alcoholic fatty liver disease.|
Sha Li, Postdoc
|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.|
Almar Neiteler, Postdoc
Almar obtained his Bachelor degree in Biology and his Master degree in Molecular Biology at Utrecht University in the Netherlands. He then obtained his PhD degree from the University of Edinburgh by establishing an in vitro model system for macular degeneration by using patient-derived induced pluripotent stem cells (iPSCs) and CRISPR/Cas9 gene editing. Almar joined Mehdi Tafti's group as a postdoctoral researcher in January 2020 to study the molecular mechanisms affected in narcolepsy and to develop an in vitro model system for this sleep disorder by using patient-derived iPSCs.
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.|
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.|
Cendrine Repond, Lab technician
Cendrine is laboratory technician associated to the group of Prof. Luc Pellerin since 2007. She obtained a CFC degree of medical technician from the Cantonal hospital in Fribourg and she also obtained a diploma of cytotechnician. During her professional career prior to join the department of Physiology, she worked in various laboratories and improved her knowledge in several areas including chemistry, cosmetic science and pathology.
She is involved in the management of the laboratory and has a good experience in molecular biology, cell cultures and microscopy. She helps all members of the group with various techniques and participate to different collaborations with external groups. She also carry her own independent research projects.
Anne-Catherine Thomas, Lab technician
Dr. Stamatina Tzanoulinou, Senior Researcher
Stamatina has received her PhD from the EPFL at the laboratory of Prof. Carmen Sandi, working on early-life stress models with a focus on reward-related and social behaviors. She then proceeded to conduct postdoctoral research with Prof. Camilla Bellone, first at the University of Lausanne, and then moving at the University of Geneva. During this appointment, Stamatina combined her behavioral expertise with whole-cell patch clamp recordings and chemogenetic approaches in order to functionally interrogate synaptic properties in autism animal models with a focus on alterations of the mesolimbic dopamine pathway. In 2020 she joined the group of Prof. Mehdi Tafti, working under the supervision of Dr. Anne Vassalli on Hypocretin/Orexin signaling circuits and relevant behaviors.
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