In FY2013: 1) We have worked toward a better understanding of prion structure by initiating the application of new (to our lab) biochemical, immunological, spectroscopic, electron microscopic, and computational approaches to defining the structure of infectious prions. We have developed new models of prion structure is being built and evaluated based on our own new data, as well as published reports. These models are based on parallel-in-register beta sheet architectures, partial versions of which have been proposed by others. These developments are in progress and are expected to lead to significant discoveries soon. 2) We have assessed the role of normal prion protein in responses to stimulators of toll-like receptor ligands and have not found any significant effects. 3) We have probed the role of normal prion protein in the experimental autoimmune encephalomyelitis in mice of the C57/BL background and found no significant effect.

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Groveman, Bradley R; Dolan, Michael A; Taubner, Lara M et al. (2014) Parallel in-register intermolecular beta sheet architectures for prion seeded PrP amyloids. J Biol Chem :
Kraus, Allison; Groveman, Bradley R; Caughey, Byron (2013) Prions and the potential transmissibility of protein misfolding diseases. Annu Rev Microbiol 67:543-64
Hasebe, Rie; Raymond, Gregory J; Horiuchi, Motohiro et al. (2012) Reaction of complement factors varies with prion strains in vitro and in vivo. Virology 423:205-13
Enquist, L W; Editors of the Journal of Virology (2009) Virology in the 21st century. J Virol 83:5296-308
Smirnovas, Vytautas; Kim, Jae-Il; Lu, Xiaojun et al. (2009) Distinct structures of scrapie prion protein (PrPSc)-seeded versus spontaneous recombinant prion protein fibrils revealed by hydrogen/deuterium exchange. J Biol Chem 284:24233-41
Caughey, Byron; Baron, Gerald S; Chesebro, Bruce et al. (2009) Getting a grip on prions: oligomers, amyloids, and pathological membrane interactions. Annu Rev Biochem 78:177-204