Grant: Project Grant

Genetic advances have led to a revolution in identifying the causes of New genetic technologies have led to a revolution in identifying the genetic causes of many human diseases, including for late onset-neurological disorders. From the discovery of so many new genes, an urgent need is the development of experimental models for preclinical research. To this end, we have worked to establish the model organism Caenorhabditis elegans as an early component of a translational therapeutic discovery program for neurodegenerative diseases. Using C. elegans models of amyotrophic lateral sclerosis (ALS) we propose to use our chemical-genetic approach to identify new modifiers of axon degeneration that may provide many new targets for therapeutic development. We will investigate genes regulating the regeneration of neurons as mechanism to protect against axon degeneration in C. elegans models of ALS. We will identify drugs that target axonal regeneration and evaluate their effectiveness in our genetic models of ALS. Finally, we will validate our findings in a higher system, namely mammalian cellular models of ALS.