NR ASAR
AU anonym
TI Structure and molecular genetics of transmissible spongiform encephalopathies - summary of ongoing research
QU UK Institute of Animal Health
IA http://www.iah.bbsrc.ac.uk/institut/public/3wplann.htm#eleven (nicht mehr vorhanden)
PT Research Report
VT
The scrapie agent is transmissible, but the chemical nature of the infectious agent remains unknown. Current theories centre on two propositions: the agent is a self-propagating conformational alteration to a normal host-encoded membrane glycoprotein PrP or that the agent is some form of sub-virus-like structure, termed a virino, with minimally a nucleic acid genome packaged in host encoded proteins. While classical biochemical evidence supports the former hypothesis, biological evidence on the existence of strains supports the latter and the resolution of this question remains the central theme of this programme. Irrespective of whether PrP turns out to be the basis for the infectious agent the protein plays a central role in the disease and a full understanding of the disease will require knowledge of the structure and function of PrP.
The programme addresses these basic questions by investigating the molecular characteristics of fractions highly purified for infectivity. Additionally PrP is being directly characterised in terms of its diversity of structure in normal and diseased tissue, its associated structural moieties which might form the basis of strain variation and its three-dimensional atomic structure. Native and recombinant PrPs and peptides based on the PrP sequence have been produced as antigens to develop polyclonal and monoclonal antibody reagents for the PrPs of different species as tools for research and diagnosis. These antibody reagents are required for studies on the cellular metabolism and trafficking of PrP in normal and scrapie-infected cells.
The protein work is complemented by analysis of the PrP gene in terms of its chromosomal organisation, the association between variant alleles and disease susceptibility or specific effects on pathogenesis and the control of its expression-both in cells in culture and in different tissues during development. These studies on the PrP gene and the role of PrP involve the development of in vitro cell systems and transgenic animal models.
SP englisch
OR Prion-Krankheiten 9