What makes a good prion?

Introduction Although transmissible spongiform encephalopathies have been studied for decades, prion biology is still a young discipline. The prion concept has existed for less than a quarter of a century, and the study of fungal prions is barely in its teens. The fascinating idea that a protein can turn into a deadly self-replicating entity attracts neurobiologists, cell biologists, geneticists and structural biologists alike. Consequently, one of the interesting features of the prion field is that it brings together people from different backgrounds. The joint Cold Spring Harbor Laboratory/Wellcome Trust Prion Biology meeting was probably the first international prion meeting intended as a cross-talk platform between mammalian and fungal prionologists. In addition to the mammalian disease-causing prions, reports dealt with the yeast [PSI+], [URE3] and [PIN+] prions, the [Het-s] prion of the filamentous fungus Podospora anserina and new fungal prions. Many fundamental questions in prion research remain unanswered (Aguzzi & Polymenidou, 2004). What is the nature and structure of the infectious agent? How do prions replicate? How do they cause disease? Work presented at the meeting from both fungal and mammalian studies provided participants with new perspectives on these questions. For example, several complementary presentations provided strong support for a crucial role for amyloid in several models of prion propagation (Weissmann, 2005). Another principal theme that emerged during the meeting was an expansion of prion biology to include new questions about the normal biological functions of prions in cells (Shorter & Lindquist, 2005). Even if the haze of mystery surrounding prions is only gradually clearing, the participants felt that much progress has been made recently in this field.