011 | Cellular and Molecular underpinnings of Sleep Homeostasis: DNA damage as sleep inductor in Drosophila

Cellular and Molecular Neurobiology

Author: Agustina Bruno-Vignolo | Email: agustinabrunovignolo@gmail.com

Agustina Bruno-Vignolo , Florencia Fernández-Chiappe , Pedro Ballestero , Luis de Lecea , Nara I. Muraro

1° Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA, CONICET – Partner of the Max Planck Society)
2° Department of Psychiatry and Behavioral Sciences, Stanford Medicine. 291 Campus Drive, Stanford, CA 94305. United States of America.

Sleep is a conserved behavior across the animal kingdom; however, the biological purpose of sleep remains a mystery. The molecular and cellular mechanisms underlying the need for sleep are still poorly characterized. With the present project we will test the general hypothesis that DNA damage accumulates during wakefulness, and is preferentially repaired during sleep. This novel hypothesis arises from recently published work in zebrafish. We propose to study the potential universality of this striking mechanism, establishing whether these causal relationships also occur in insects. Using the experimental advantages offered by Drosophila melanogaster, we have developed a thermogenetic assay that demonstrates that neuronal activation promotes the need for sleep in flies, and is accompanied by DNA damage. At the molecular level, in fish it has been reported that the protein Parp1, which binds to DNA damage sites and participates in their repair, is necessary to promote sleep. Since the molecular components of the DNA damage response show high evolutionary conservation, we will test whether proteins involved in DNA repair mechanisms in Drosophila are also molecular components that regulate sleep homeostasis. Our experiments will shed light on the relationship of DNA repair and sleep homeostasis throughout evolution, and may lead to new interventions to treat sleep disorders, improve sleep efficiency and brain function.