U.S. Department of Health and Human Services
Herman Edskes
 

 Contact Info

 
Tel: 301-496-1309
Email: edskes@helix.nih.gov
 

 Select Experience

 
  • Research FellowNIH2000-2001
  • Postdoctoral FellowNIH1995-1999
  • Ph.D.University of Kentucky1994
  • M.Sc.Wageningen University1990
 

 Related Links

 
Specialties
  • Genetics/Genomics
  • Microbiology/Infectious diseases (non-viral)
  • Molecular Biology/Biochemistry
  • Prions
  • Virology
Research Summary/In Plain Language

Research in Plain Language

Starting in the late 1980s and continuing into the late 1990s, many newspapers featured front-page stories about mad cow disease (or bovine spongiform encephalopathy). An unusual agent causes the infectious mad cow disease. This agent is a misfolded protein, not a virus or a bacterium. Such proteins are called prions (pronounced pree-ons).

Mad cow disease belongs to a group of prion diseases called transmissible spongiform encephalopathies (TSEs). TSEs are fatal diseases that break down cells of the brain and nervous system. TSEs also include the human diseases kuru and Creutzfeldt-Jakob disease. In TSEs, enzymes no longer break down a particular protein. As a result, these proteins bunch together through a process called protein aggregation. This process results in a substance called an amyloid. In humans, TSE diseases are rare, but amyloid deposits occur in much more prevalent diseases, such as Alzheimer’s and Parkinson’s. Health experts and the public have expressed concern about mad cow disease transmission to people.

Mammals are not the only organisms with prions. These infectious proteins also occur in fungi. In 1994, Dr. Reed Wickner showed that the [URE3] element of the yeast Sacchromyces cerevisiae (S. cerevisiae) is a prion of the Ure2 protein. The [URE3] prion is an infectious form of amyloid comprised from Ure2 protein. Scientists have demonstrated that several more proteins form a prion in S. cerevisiae. Most of these prions result from a yeast protein that forms amyloid. However, not all prions are based on amyloid formation.

Both mammalian and fungal prions can form strains with distinct biological properties. These are called variants for the fungal prions. In amyloid filaments, the Ure2 protein folds in a particular way to form a structure called a sheet. Variants arise from different folds of the sheets and from the sheets at different positions. To visualize this, imagine pouring syrup on a pancake. You make a pattern going from top to bottom, while at the same time making left and right movements. Cut away all parts of the pancake not covered with syrup. Make several exact copies and stack them on top of each other. This is your amyloid filament. When you vary the left and right movement, it is easy to see different patterns. These represent different amyloids.

Our research group studies [URE3] and other yeast prions. We try to understand how proteins form infectious elements. We are also very interested in the cellular machinery that facilitates prion formation. Another area of research examines how prions affect cells. Studying yeast prions enhances our understanding of similar infectious elements present in animals and people.