My laboratory employs yeast models to study prions and amyloids. Prions were initially identified as proteins in an unusual conformation that cause infectious neurodegenerative diseases, such as "mad cow" disease, kuru or Creutzfeldt-Jakob disease. Infection depends on the prion's ability to convert a non-prion protein, encoded by the same host maintenance gene, into the prion conformation. Prions form ordered cross-beta fibrous aggregates, termed amyloids. A variety of human diseases, including Alzheimer's disease, are associated with amyloids and possess at least some prion properties. Some amyloids have positive biological functions. Many proteins can form amyloids in specific conditions. It is thought that amyloid represents one of the ancient types of the protein fold. Some yeast non-Mendelian heritable elements are based on a prion mechanism. This shows that heritable information can be coded in protein structures, in addition to information coded in DNA sequence. Therefore, prions provide a basis for the protein-based inheritance in yeast (and possibly in other organisms).
Major topics of research in my lab include cellular control of prion formation and propagation (with a specific emphasis on the role of chaperone proteins), and development of the yeast models for studying mammalian and human amyloids, involved in diseases. Our research has demonstrated that prions can be induced by transient protein overproduction and discovered the crucial role of chaperones in prion propagation, shown evolutionary conservation of prion-forming properties, established a yeast system for studying species-specificity of prion transmission, and uncovered links between prions, cytoskeletal networks and protein quality control pathways.