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Understanding prion strains and species barriers and devising novel diagnostic approaches

Project information

Grant agreement ID: 23183

  • Start date

    1 November 2006

  • End date

    30 April 2010

Funded under:

FP6-FOOD

  • Overall budget:

    € 2 395 308

  • EU contribution

    € 2 158 500

Coordinated by:

THE HEBREW UNIVERSITY OF JERUSALEM

Israel

Objective

The existence of stable strains of prions, differing in incubation times, clinical features, and neuroanatomical PrPSc deposition, is disquieting. The structural and biological features which encode strains and determine their disease phenotype are obscure. Some strains, including BSE, easily traverse species barriers causing serious concerns in the EU. Promiscuous strains present a public health threat if they propagate through the food chain, while remaining either undetected or misidentified. These dangers are illustrated by the atypical cases of scrapie which have appeared throughout the EU, including in sheep hitherto considered genetically resistant, and by the identification of BSE in a goat in France. As yet there are no diagnostic procedures to identify TSE strains, except in some rare cases. We propose studying fundamental and applied aspects of prions strains and their relationship to the species barrier, and to use the knowledge generated to initiate diagnostic methodologies to detect strains and predict their epidemiological behaviour. We have assembled a powerful consortium of partners with proven experimental and industrial achievements. We will (i) systematically examine the properties of field strains and their species barriers when propagated (ii) examine strain-dependent biochemical and biophysical properties of PrPSc (iii) apply novel cryoelectron tomographical techniques to determine the 3-D structure (at 4 nm resolution) of PrPSc in various strains in neuronal (stem) cells (iv) study strain-specific features of prion infection in cultured cells, including their uptake receptors, (v) characterize strain dependent cytopathogenic mechanisms in infected cells. We will prepare novel diagnostic and research reagents such as a) possibly strain specific, PrP monoclonal antibodies, b) a goat PrP transgenic mouse, and c) novel ovine, caprine and bovine neuronal stem cells susceptible to prion infection.

Coordinator

THE HEBREW UNIVERSITY OF JERUSALEM

Address

The Authority For Research And Development, Edmond J. Safra Campus, Givat Ram
Jerusalem

Israel

Participants (10)

HET NEDERLANDS KANKER INSTITUUT

Netherlands

KAROLINSKA INSTITUTET

Sweden

UNIVERSIDADE DE SANTIAGO DE COMPOSTELA

Spain

INSTITUT PASTEUR

France

INSTITUTO NACIONAL DE INVESTIGACION Y TECNOLOGIA AGRARIA Y ALIMENTARIA

Spain

MABGENICS GMBH

Germany

INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE

France

NATIONAL VETERINARY INSTITUTE (SVA)

Sweden

THE VETERINARY LABORATORIES AGENCY OF NEW HAW, ADDLESTONE, SURREY, KT15 3NB

United Kingdom

HEINRICH HEINE UNIVERSITY OF DUESSELDORF

Germany

Project information

Grant agreement ID: 23183

  • Start date

    1 November 2006

  • End date

    30 April 2010

Funded under:

FP6-FOOD

  • Overall budget:

    € 2 395 308

  • EU contribution

    € 2 158 500

Coordinated by:

THE HEBREW UNIVERSITY OF JERUSALEM

Israel