Projects / Programmes
Prion diseases and their diagnostics
Code |
Science |
Field |
Subfield |
3.03.00 |
Medical sciences |
Neurobiology |
|
Code |
Science |
Field |
B500 |
Biomedical sciences |
Immunology, serology, transplantation |
B640 |
Biomedical sciences |
Neurology, neuropsychology, neurophysiology |
B750 |
Biomedical sciences |
Veterinary medicine: surgery, physiology, pathology, clinical studies |
B210 |
Biomedical sciences |
Histology, cytochemistry, histochemistry, tissue culture |
B490 |
Biomedical sciences |
Haematology, extracellular fluids |
B120 |
Biomedical sciences |
Molecular biophysics |
P310 |
Natural sciences and mathematics |
Proteins, enzymology |
T490 |
Technological sciences |
Biotechnology |
monoclonal antibodies, prions, prion diseases, diagnostics, genotyping, NMR
Researchers (21)
Organisations (4)
Abstract
Prioni diseases represent a threat to public health, while their effect on European economy amounts to billions of dollars. Due to the long incubation period and the unknown mode of the interspecies transfer and advancement of the disease it is impossible to asses accurately the extent of threatening epidemics in humans. Reliable diagnostics is therefore of extreme importance to prevent spreading of prioni diseases. All currently available diagnostic tests are based on antibodies which do not distinguish between normal (PrPc) and pathological form of prion protein (PrPSc). Ideal test should be able to distinguish between the two forms, which would make it simple, fast and also less expensive. Based on monoclonal antibodies (MAbs), prepared at the Blood Transfusion Centre of Slovenia against a peptide fragment chosen from the primary structure of a human PrP, we will develop and validate a reliable test for diagnostics of prion diseases within the scope of the proposed project. Furthermore, we will use different MAbs for research of human and animal prion proteins in various tissues and body fluids, in the first place in human blood. We will determine the frequency of the codon 129 polymorphism of PrP gene in Slovenian population and try to evaluate its role in the prion disease. MAbs will be also used for research of molecular mechanisms of recognition of different forms of PrP. Based on NMR experiments on isotopically labelled peptide, we will monitor its conformation in complex with different antibody fragments, which recognize either native or pathologically modified protein. This will allow us to infer the conformation of pathologically modified protein or the conformational change, which causes the aggregation of prion protein on the onset of the disease. We will also investigate the response of prion protein to changes in solution conditions, such as pH, polarity of the solvent, ionic strength etc..