A comprehensive functional analysis of Dup15q genes: phenotypic effects and treatment following restoration
Awardee: Alon Zaslaver
Institution: The Hebrew University
Grant Amount: $47,038
Funding Period: February 1, 2025 - January 31, 2026
Summary:
Dup15q syndrome is genetically inherited and is caused due to an extra copy of a piece of chromosome 15. As a results, the genes located on that chromosome region are expressed at higher levels. However, it is less clear which genes contribute to the various observed deficits. Moreover, unless genetically tested during pregnancy, children with Dup15q are typically diagnosed only at the age of ~2 years old. Thus, new therapeutic approaches need to focus on improving and restoring functional deficits after most embryonic neurodevelopmental processes are complete. To address all these needs, we will use the powerful genetic model system (C. elegans worms). Specifically, we carefully designed an experimental genetic system which allows mild and fine upregulation of individual and combinations of Dup15q genes during neurodevelopment, and restoration of the elevated expression to normal levels at the adult stage of the animal. To analyze neurodevelopmental deficits, we will use state-of-the-art experimental techniques including functional imaging of neural activity and behavioral assays. These efforts will reveal the individual and sets of genes that lead to neurodevelopmental phenotypes, and most importantly, whether restoration of gene expression to normal levels, can improve these phenotypic deficits. Such findings may pave the way to novel interventions and therapeutic approaches.