Description

To work properly, most proteins in the human body must adopt a three-dimensional shape, their so-called native state. However, under certain circumstances, they change into an amyloid state, which is a toxic structural form where they aggregate into protein clusters (“prions”). In the past, this conformational change was observed in neurodegenerative diseases, as for example Mad Cow disease, Creutzfeldt-Jakob disease and Alzheimer’s disease. Recently, it has been shown that such protein aggregates could also play an important role in cancer, as the “Guardian of the Genome”, the tumor suppressor protein p53, can aggregate into “infectious” prions (“p53 prions”). Furthermore, recent data demonstrated the high potential of p53 prions as a biomarker for patients’ survival in ovarian cancer. However, commercially available reliable assays which allow the quantitative analysis of p53 prions are lacking. The aim of the proposed project is to develop a diagnostic test for the quantification of p53 prions and to evaluate if exosomes, which are cell-derived vesicles and extensively distributed in various biological fluids, are vehicles for p53 prions and can be used as diagnostic targets. First, we will establish novel methods to isolate and enrich for ultrapure exosomes from ascites fluid and blood (size-exclusion-chromatography, Fab-TACS® technology). Second, a highly innovative assay, based on the proximity ligation assay technology, that allows specific detection and quantitative measurement of p53 prions will be developed. Finally, a method, which combines magnetic bead-based characterization of exosomes and the p53 prion quantification test, will be developed.

Funding: Country of Lower Austria, EFRE

Details

Duration 01/01/2021 - 31/12/2021
Funding Bundesländer (inkl. deren Stiftungen und Einrichtungen)
Program
Department

Department for Biomedical Research

Center for Biomedical Technology

Principle investigator for the project (University for Continuing Education Krems) Mag. Rene Weiss, PhD

Project Manager

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