Grant: Project Grant

Prion disorders are incurable diseases of the ageing brain that affect both humans and animals. Examples include Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep, chronic wasting disease in deer and elk, and "mad cow disease". In prion disease, a protein (the "prion protein") clumps together in the brain to form aggregates called prions. Prions cause the death of brain cells and are able to spread within the brain. Under certain circumstances, prions can also transmit disease between people or animals. However, most cases of prion disease in humans do not result from infection but instead occur due to the spontaneous formation of prions in the brain. Little is known about the initial events that cause the prion protein to clump together to form prions, and we currently lack the appropriate tools to study this process. Moreover, understanding the earliest events in prion disease is likely to be crucial for the development of effective therapies. In this proposal, we will use genetically-engineered cells and mice to re-create and study the initial events that cause the prion protein to clump together in prion disease. In particular, we will take advantage of the unique properties of the prion protein from the bank vole, a rodent that is especially susceptible to prion disease. These studies will provide new tools for studying prion disease and will uncover new strategies for treating these devastating disorders.