David Harris and Heather True-Krob study prions, a new kind of infectious agent thought to be at the heart of several rare neurodegenerative disorders that devastate the brains of humans, cows and sheep.

Harris and True-Krob are gaining insight into how prions form and cause disease, and as they do, tantalizing hints are starting to emerge that prions may be connected to a much wider range of biological phenomena than the rare brain disorders that first led to their discovery.

The prion consists entirely of a misfolded protein. The prion perpetuates itself by influencing nearby normal copies of the same protein, somehow increasing the chances they will misfold and become prions. In cows with mad cow disease, sheep with scrapie, and humans with Creutzfeldt-Jakob disease, this misfolding causes a cascade that results in protein aggregates which then form dense plaque fibers that lead to microscopic “holes” in brain tissue, causing physical and mental degeneration, and death.

Harris conducts the bulk of his research in approximately 50 lines of mice genetically modified to produce prions. True-Krob specializes in the study of yeast prions, which don’t affect humans and other mammals but have similar structural elements.