José A. Rodriguez, Ph.D.

Research

The Rodriguez lab will explore the range of structures adopted by prions—a form of infectious protein that causes neurodegenerative disorders such as Creutzfeldt-Jakob disease. Prion proteins—like the amyloid proteins associated with Alzheimer’s disease—form large clumps that damage and ultimately kill neurons in the brain. It is not known, however, what causes prions to switch from their harmless, normal conformation to the infectious aggregate-forming structure. As a postdoctoral fellow, I pioneered methods for the collection of structural data from tiny protein “nanocrystals”—techniques our lab now uses to determine the detailed structures of amyloid proteins. Now, combining this technique with methods in physical chemistry and molecular and computational biology, we will analyze the range of structures that prion proteins adopt within a single nanocrystal. The findings could reveal the structural changes that transform prions into their toxic, infectious form—and lead to novel strategies for the treatment of neurodegenerative disorders associated with the formation of amyloid aggregates.