Department of Infectious Diseases
Adjunct Professor, Dept. of Chemistry & Biochemistry, Florida Atlantic University
Molecular Biology of Prions
The principal component of the transmissible agent of spongiform encephalopathies, the prion, is believed to be a conformational variant of the ubiquitous host protein PrPC, and the different properties of various prion strains are attributed to distinct abnormal conformations of this protein. The precise structure of the prion is not known, nor are the mechanisms of infection, conformational conversion and pathogenesis understood.
Many aspects of prion diseases must be studied in animal models, but because they take many months to develop, the molecular processes underlying the replication and spread of prions are best investigated in cell culture. We have isolated cell lines that are extremely sensitive to prion infection and have established an in vitro prion assay that is more sensitive than the traditional mouse bioassay and ten times faster. Using this assay we are trying to generate prion infectivity in vitro, from non-infectious components. We are studying the mechanism by which prions infect cells, the prerequisites for susceptibility to infection and the mechanism by which infectious particles are released by cells.
M.D., Medicine, University of Zurich, 1956
Ph.D., Organic Chemistry, University of Zurich, 1961
Fellow of the American Academy of Microbiology
Betty and David Koetser Award (Zürich, 2001)
Fellow of the Academy of Medical Sciences (London, 2001)
Friedrich-Bauer-Prize for Medical Research(University of Münich, 2001)
Member of the Board of Governors of Tel AvivUniversity (since 1997)
Member of the Editorial Board of the Proceedings of theRoyal Society (since 1999)
Member of Board of Directors of Speedel (since 2003)
Member of the Scripps Board of Scientific Governors (2004)
Honorary Senior Fellow, Institute of Neurology, UniversityCollege London (2004)
Warren Alpert Foundation Prize (Harvard Medical School,September 2004)
Foreign Associate of the U.S. National Academy of Sciences
Foreign Member of the Royal Society
Awarded over 20 prizes
E. Flechsig, I. Hegyi, M. Enari, P. Schwarz, J. Collinge and C. Weissmann, Transmission of scrapie by steel-surface-bound prions. Molecular Medicine 7, 679-684 (2001).
E.Flechsig, I.Hegyi, R.Leimeroth, A.Zuniga, A.Cozzio, P.Schwarz, T.Rülicke, J.Goetz, A.Aguzzi and C.Weissmann, Expression of truncated PrP targeted to Purkinje cells of PrP knockout mice causes Purkinje cell death and ataxia. EMBO J. 22, 3095-3101 (2003).
P.-C.Kloehn, L.Stoltze, E.Flechsig, M.Enari and C.Weissmann, A quantitative, highly sensitive cell-based infectivity assay for mouse scrapie prions. PNAS, 100:11666-71 (2003).
L.Anderson, D.Rossi, J.Linehan, S.Brandner and C.Weissmann, Transgene-driven expression of the Doppel protein in Purkinje cells causes Purkinje cell degeneration and motor impairment. PNAS, 101, 3644-49 (2004) .