We know that sleep is fundamental for brain development and plasticity. We know that many features of sleep are inherited and that genes play an important role in sleep physiology. However, we are missing some fundamental regulatory mechanisms of this phenomenon. Therefore, in the GEB lab we study epigenetic mechanisms of sleep in which we deal with two fundamental aspects:

• epigenetic variation early in life that impacts on sleep;
• parental genomes that control sleep in mammalian brain.

In particular, we investigate genomic imprinting and sleep. This parent-of-origin issue was never considered in sleep and circadian studies before. Imprinting is well-known in epigenetics as a mark across the genome causing monoallelic expression and at the simplest imprinted loci maternally or paternally inherited allele are transcriptionally silenced. We proposed the hypothesis that imprinting has set an evolutionary agenda for the physiology of mammalian sleep (Tucci, PLoS Genet., 2016; Tucci et al., Cell, 2019).

Data from ancient genomes with different geographic transects are becoming useful tools to interrogate evolution. In this new territory of comparative paleogenomics, an intriguing area of investigation is the possible trade-offs of some past positive selections that today are associated with maladaptation, such as obesity and sleep/circadian disorders. All this has motivated our group to explore positively selected variants of imprinted genes that contain evidence of mutations that were fixed in the genome of modern humans.

Imprinting has been instrumental to study epigenetics of sleep and, incidentally, brought us to generate novel technologies of gene editing, which can be used for a wide range of applications.