Thesis defense Mireia Coll Tané (Donders series 571)

22 September 2022

Promotors: prof. dr. A. Schenck, prof. dr. B. Franke

Characterizing and targeting sleep disturbances in neurodevelopmental syndromes – insights from Drosophila
Sleep disturbances are pervasive in individuals with autism spectrum disorder (ASD) and intellectual disability (ID), and they inflict severe negative effects on the individuals experiencing them and their families. Despite the availability of effective behavioral therapies for typically developing individuals diagnosed with sleep disorders, these are rarely applied to individuals with neurodevelopmental disorders. This may be due to the belief that ASD/ID-associated sleep disorders are treatment-resistant. Thus, there is a pressing need to further investigate the reversibility of sleep disturbances and to characterize their underlying (patho)mechanisms in individuals with neurodevelopmental disorders, such as ASD and ID.
In my doctoral thesis, I provide novel insight into the sleep pathophysiology of multiple Mendelian neurodevelopmental syndromes taking advantage of the versatile animal model Drosophila melanogaster (the fruit fly). With this strategy, I was able to provide novel evidence for the role of the ASD/ID genes CHD8/CHD7, KMT2C, and EHMT1 in sleep regulation. Furthermore, I was able to dissect their cellular and temporal dynamics as well as their underlying mechanisms. Lastly, despite their developmental origin, I show that ASD/ID-related sleep defects can be reversed in adulthood by a readily-translatable behavioral regime resembling human sleep-restriction therapy, highlighting that sleep problems are treatable.