The research, I plan to do, will be designed to study the interaction of huntingtin with other proteins in the brain and to investigate how expanded polyglutamines (polyGln) in huntingtin may alter its interactions with other proteins. More specifically, I plan to: 1. Purify functional HD protein (huntingtin) from brain or from a yeast expression system in biochemically significant quantities; 2. Identify potential binding proteins of the HD protein and to study the physiological consequences of their binding; 3. Study the interaction of the calmodulin huntingtin association mediator protein (CHAMP) with normal and mutant huntingtin and investigate how their interaction is regulated by calcium and calmodulin. 4. Purify, clone, sequence, and characterize CHAMP.