The SAS proposals for participation in FP6 projects
are listed in blocks according to the FP6 priority theme structure

FP6 priority
1.1.1   Genomics and Biotechnology for Health
Title of the proposal

Evaluating the mechanisms of an eventual BSE transmission in susceptible and resistant sheep

Slovak Academy of Sciences, Institute of Neuroimmunology, National Reference Laboratory for TSE
Dubravska cesta 9, 842 45 Bratislava, Slovak Republic
+421 2 54788100

Research subject for a potential FP6 project

Conformational diseases (e.g. BSE, Alzheimer’s disease) represent heterogenous etiological entity affecting predominantly neuronal and brain tissues. Ther nature of these diseases consists in the conformational transition of physiological protein into its pathological variant. At the amino acid level both variants – physiological and pathological – are identical. Molecular events associated with such structural changes are largely unknown. Monoclonal antibodies are optimal tool for analysis of even subtle conformational differences between proteins. We have long years experiences with preparation and exploatation of monoclonal antibodies for structural immunoanalysis of pathological tau protein in Alzheimer’s disease. In general, such attitude allows to gain relevant information for elucidation of structural requirements relevant for inducing confor-mational changes of any protein.
We would like to use our know-how for the study of conformational modification associated with transition of cellular prion into diseased scrapie prions in sheep and in model mouse system. Species barrier has appeared to be efficient for limiting propagation of TSE agent between animals. BSE strain seems to have a particular ability to easily cross it and could be transmitted between sheep following similar scheme than scrapie. We intend to assess structural modification after adaptation of BSE strains following subpassages in sheep. Eventual antigenic modifications of the BSE strain will be studied directly from sheep. We would like to use these findings for the development or the validation of tools (biochemical or bioassay) susceptible to differentiate BSE and scrapie in co-infected sheep.

Recent international cooperation of the research team

Prionics AG, University Zurich, Switzerland
International School for Advanced Studies (SISSA), Trieste, Italy
New York State Institute for Basic Research in Developmental Disabilities, Staten Island, USA

Proposer´s relevant publications related to the research subject

Novak M., Vrtiak O.J., Mikula I., Tkacikova L (2000): Ovine Scrapie: Priorities and Importance. Folia Microbiologica 45 (6), 475-483 (2000)
Cattaneo A., Capsoni S., Margotti E., Righi M., Kontsekova E., Pavlik P., Filipcik P., Novak M. (1999): Functional blockade of tyrosine kinase A in the rat basal forebrain a a novel antagonistic anti-receptor monoclonal antibody. Journal of Neuroscience 19, 9687-9697
Ferencik M., Novak M., Mikula I., Sokol J.(1998): Prionoses: Neurodegenerative diseases induced by prions. Bratislava Medical Journal 99, 486-498