This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Prion protein diseases, such as mad cow disease, scrapie, and Creutzfeldt-Jakob disease, are neurodegenerative protein-folding diseases that involve the misfolding of naturally occurring proteins in the brain. The function of the prion protein is not known, but it is thought to play a role in copper homeostasis. Recently, the process of prion-misfolding has been associated with the binding of metal ions such as iron, copper and zinc;yet, these interactions are poorly understood. To date, metal concentrations in prion-infected brain tissue are generally measured via macroscopic (bulk) techniques, such as atomic absorption or ICP-MS, which do not provide any spatial information on localized metal accumulation.