PROJECT SUMMARY Disease and injury cause a catastrophic loss of cognitive and motor abilities in the nervous system. Preventing neurodegeneration is critical to maintaining neuronal function. To develop effective treatments, we first need a greater understanding of the genetic and cellular mechanisms that determine whether the nervous system degenerates in response to various insults. Caenorhabditis elegans is a highly tractable model to dissect conserved molecular and cellular mechanisms. The goal of this proposal is to take advantage of the C. elegans model to identify regulatory mechanisms of axon degeneration. To reach this goal, I will apply my developing skills in detailed genetic analyses, laser axotomy, imaging, sequencing, and bioinformatics. The impact of this project is significant. In addition to providing a critical advance in understanding the fundamental mechanisms of neurodegeneration, it will also inform future therapeutic approaches that can be manipulated to protect the nervous system from degenerating.