In Vivo CRISPR to Uncover Determinants of Neurodegeneration

This project will develop a new high-throughput in vivo (mouse) CRISPR/Cas9 method to screen for genetic modifiers of Spinocerebellar ataxia in the adult mouse brain. While most CRISPR screens are done in cell culture, this in vivo approach in the adult mouse — while significantly more complex — has the advantage of better capturing the complex interactions of neurons within their native physiological environment. The team plans to validate the results of the screen functionally as well as test in other neurodegenerative disease models to uncover shared and unique pathways. This project was selected for the second phase of the Collaborative Pairs RFA.