Dr. Paulson examines the causes of age-related neurodegenerative diseases and develops treatments for them. In this award, he will investigate how the ubiquitin signaling system is implicated in diseases of the nervous system. In neurodegenerative diseases, proteins in these signaling systems are particularly prone to phase-separating and aggregating. Dr. Paulson will examine the impact of altered ubiquitin signaling in the nucleus, the contribution of altered ubiquitin homeostasis to selective cell type and regional vulnerability, and the relationship between mutation-induced changes in disease proteins, altered function in ubiquitin-linked pathways, and toxicity in the nervous system. His work will define the ubiquitin’s roles in nervous system diseases and identify promising therapeutic targets for neurodegenerative diseases.