Design and Validation of Autophagy Targeting Chimeras (AUTAC)

This proposal describes a project at the interface of computational modeling, chemistry and
biology. We aim to develop a novel class of chemical compounds for probing the regulation of
autophagy in cells and tissues. Specifically, we aim to develop compounds that are based on
PROteolysis TArgeting Chimera (PROTAC) design. PROTACs are chimeric small molecules that
link a cargo protein to the proteasomal degradation machinery, allowing degradation of the
cargo in the proteasome. We plan to design novel PROTACs that mediate lysosomal
degaradation of cargo, allowing applications for the degradation of much larger
macrocomplexes in cells such as mitochondria.