Final Activity Report Summary - SIMODSS (Single molecule dynamics of stress signalling components studied with the ulta-sensitive fluorescence microscope Cytoscout for drug screening)
The project brought together an academic research institution, providing key expertise in Hsp function (Biological Research Center of the Hungarian Academy of Sciences (BRC)) and an applied research partner focusing on exploring the potential of single molecule techniques (Upper Austrian Research GmbH (UAR)). As a first objective an ultra-sensitive fluorescence microscope in order to visualize single fluorescently labelled molecules was installed at BRC. This large area ultra-sensitive microscopy was then applied to explore timecourses of Hsp upregulation induced by physiological heat stress for a large number of cells at the level of individual cell and will in the future be applied to study variations in Hsp expression levels upon dependent on compounds added. This laid the foundation for membrane-based drug screening assays, which are based on the expertise of both host organisations. As a parallel objective a model system that allowed studying the upregulation of Hsps in cancer cells upon stress was established at UAR.
This model system was ideally suited for the available ultra-sensitive microscopy platform and allowed for the first time to decouple the effects of stress and elevated intracellular Hsp70 on the surface exposure of this chaperone. The found data are relevant for the protective and immune stimulatory role of Hsp70 exposed on the cellular surface.