Chiara CirelliChiara Cirelli

 

 

Function of Sleep Using Molecular and Genetic Approaches

E-mail: ccirelli@wisc.edu

Departemental Phone: (608) 263-0491

Research Strengths: Behavior: Cognition and Emotion, Molecular Neuroscience

All animal species studied so far spend a large portion of their life asleep, even if doing so is potentially dangerous. The amount and quality of sleep are tightly regulated - sleep pressure increases the longer one stays awake, and becomes overwhelming after prolonged sleep deprivation. Sleep loss leads to cognitive impairment and, if prolonged for several weeks, to death. Thus, sleep appears to fulfill some fundamental function, but what this function may be remains unknown.

Understanding the function of sleep and clarifying the functional consequences of sleep loss are not just issues of theoretical interest: the National Highway Traffic Safety Administration estimates conservatively that each year drowsy driving is responsible for at least
100,000 automobile crashes, 71,000 injuries, and 1,550 fatalities (National Sleep Foundation, 2002). Current pharmacological attempts at reducing the need for sleep or at making sleep more restorative are hampered by the lack of knowledge of its basic mechanisms and functions. Specifically, the identification of new targets for drug development requires a mechanistic understanding of how sleep is regulated at the cellular level.

My research is aimed at investigating the fundamental mechanisms of sleep by using a combination of molecular and genetic approaches. The molecular approach consists in whole-genome profiling studies to identify all the genes whose expression changes in the brain in sleep
relative to spontaneous wakefulness and sleep deprivation. For the past several years, we have pursued such genome-wide screening mainly in rats, fruit flies, hamsters and, most recently, humans. Our laboratory has recently been able to identify genes that are specifically activated
in the brain of a sleeping animal. These new results suggest that sleep may be especially important for internal membrane trafficking in neural and glial cells. These findings prompt new hypotheses about the functions of sleep that need to be examined through follow-up functional
studies.

A second, complementary approach to the functions of sleep exploits the power of Drosophila genetics. Over the past 4 years, we have demonstrated that fruit flies sleep and need sleep in much the same way as we and other mammals do. This finding has opened the way to the genetic dissection of sleep using mutant screening and other powerful tools for genetic manipulation that are available in Drosophila. We have set up a laboratory to perform large-scale mutagenesis screening for sleep phenotypes in Drosophila. The goal is to identify flies that need little sleep as well as flies that are resistant to sleep deprivation. Over the last 2 years, we have screened more than 8000 mutant lines, each carrying a mutation in one single gene, and identified ~ 10 candidate lines that either sleep very little or are resistant to sleep deprivation. We are now performing the necessary molecular and genetic characterization of such mutant lines. The final goal is to identify the cellular mechanisms that allow these mutant flies to be continuously awake and perform well while requiring little or no sleep.

Website:

http://tononi.psychiatry.wisc.edu/People/ChiaraCirelli.html

Selected Publications:

    
         
   

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