Seeger Brunner
Fakultäten » Medizinische Fakultät » Neuropathologie, Institut für » Prof. Dr. Adriano Aguzzi » Seeger Brunner
Completed research project
| Title / Titel | Identification of Marker Proteins for Prion Disease in Urine | ||||||
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| Abstract (PDF, 14 KB) | |||||||
| Summary / Zusammenfassung | To date, definite diagnosis of prion disease can only be by made by analysis of tissue samples. A sensitive in vivo assay for prion disease, using easily available materials such as blood or urine, would have tremendous advantages. Recently a protease resistant isoform of the prion protein, denominated UPrPSc, was reported in the urine of scrapie-infected hamsters, BSE-infected cattle and humans suffering from Creutzfeldt-Jakob disease (Shaked et al. 2001). The aims of our study are to find out whether a similar form of UPrPSc exists in the urine of scrapie-infected mice. If this is the case, we intend to develop a test for this molecule using a highly sensitive quantitative proteomics approach. The test design will also allow us to investigate the dynamics of the appearance and quantitative excretion of this protein during the incubation period and disease progression. In a second approach we want to compare the entire proteome contained in the urine of scrapie infected mice with those of a mock-infected control group. This will again be done by quantitative proteomics. The rationale is to identify proteins that are differentially excreted in scrapie-infected mice compared to controls. The identification of a marker protein for prion disease would allow to identify infected individuals and to make the diagnosis of scrapie as early as possible. Mice of the experimental group will be inoculated with RML brain homogenate. For each experimental group there will be a mock-inoculated age- and strain-matched control group. We will perform the experiments on four different inbred mouse strains. Urine from the mice will be collected every 14 days until they succumb to the disease. Total protein will be extracted and UPrPSc will be quantified using mass spectrometry. In the second approach the protein samples from the experimental group and the control group will be labeled using the ICAT-method (Gygi et al. 1999). This technology, in combination with mass spectrometry, will allow us to identify quantitative differences of proteins in the urine of scrapie-infected and control animals. The sensitivity of the newly identified markers will be directly compared to that of the UPrPSc-assay. |
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| Project leadership and contacts / Projektleitung und Kontakte |
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| Other links to external web pages | http://www.uzh.ch/pathol/neuropathologie/d/index.html | ||||||
| Funding source(s) / Unterstützt durch |
Forschungskredit der Universität Zürich, Other Public Sources (e.g. Federal or Cantonal Agencies) Department of Defense, USA |
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| Duration of Project / Projektdauer | May 2002 to Apr 2006 |