How do "rotein-only" prions achieve strain variations? And what is the use of a prion? These are the questions we would like to answer.
We have demonstrated that strains of the yeast prion [PSI] are differently folded amyloid fibers of the Sup35 protein, making clear that the problem of prion strains and the enigma of amyloid structures are deeply connected. Amyloid fibers are associated with about twenty human disease conditions including Alzheimer's disease and Huntington's disease. In these diseases, different proteins aggregate to adopt a characteristic cross-b folding pattern with β-strands lying perpendicular to the fiber axis. It is puzzling how such a generic structure can provide sufficient specificity for distinctive prion strains to truthfully propagate. We have discovered that different amino-acid patches in the Sup35 protein are responsible for the construction of different [PSI] strains. We will determine how these patches are selectively recruited for each prion strain.
While prions are amyloid, the converse is not always true. Complex interplays between amyloid conformations and appropriate cellular co-factors determine whether an amyloid structure can propagate as a prion inside cells. We are creating artificial cellular environment in yeast to elucidate these intricate interactions.
Although nature has been using prions for a long time, man only begins to understand their utility. We are very interested in discovering new prions and elucidating their roles in cellular control. We will also exploit prions to engineer novel activities in a cell. This line of research could lead to novel biotechnological applications.