This suggests that DREAM inhibitors are first-in-class potential sleep mimetics. To learn more, check out our updated preprint. Kudos to Isabela Santos Valentim, the first author, and all the collaborators who invested time and huge effort in this study!!

Good news - we can reverse the effects of sleep disruption with genetic and pharmacological DREAM inhibitors, fully restoring the health of permanently sleep-disrupted animals (at least in the C. elegans system).

Conversely, during sleep, DREAM levels are lowered, leading to chromatin opening and allowing repair to take place. With sleep deprivation, DREAM stays unregulated and chromatin remains closed, causing repair to erode over time and leading to cellular dysfunction.

During wakefulness, DREAM levels increase, leading to chromatin condensation. This protects genomic DNA from wakefulness-associated damage but, on the other hand, suppresses repair activities that require gene expression.

Combining multi-omics, genetic, and functional assays across systems, we found that the chromatin remodeling complex DREAM (an abbreviation unrelated to sleep) is a central regulator of closed and open chromatin states during wakefulness and sleep, respectively.

We are currently working to secure funding for a human clinical study. Fingers crossed!

This makes so much sense: we had the same conclusion in my postdoc paper where we found that germline DNA damage promotes somatic stress tolerance. We could exactly link it to delayed reproduction due to need of germline DNA repair.