Adapting targeted protein aggregation for detection.

Protein aggregation is a protein assembly process akin to crystalisation that is mediated by the formation of intermolecular beta-structures by short aggregation prone sequences of the aggregating protein. Steric compatibility between side chains in the tightly packed spine of the aggregate are thought to confer specificity to this process as heterologous interactions will disturb the regularly repeating packing patterns. As a result, self aggregation is strongly preferred over co-aggregation, rationalising the strong enrichement in a single protein in the proteinaceous precipitates observed in human aggregation diseases such as Alzheimer disease. In the current proposal, we aim to develop methods that exploit the beta-aggregation principle for the specific detection in vitro or in vivo of desirable protein analytes in a collaboration between the aggregation specialists at the Switch Laboratory (Prof Rousseau & Schymkowitz), with the experts of diagnostic assays at the clinical laboratory of the University Hospital (Prof Van Eldere) as well as the in vivo imaging experts of the radiopharmacy group (Prof Bormans).