SIMODSS · Single molecule dynamics of stress signalling components studied with the ulta-sensitive fluorescence microscope Cytoscout for drug screening
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2004-07-01 → 2008-06-30
- EU contribution
- €240,233
- Participants
- 2
- Scheme
- TOK
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Results in brief
Final Activity Report Summary - SIMODSS (Single molecule dynamics of stress signalling components studied with the ulta-sensitive fluorescence microscope Cytoscout for drug screening)
The overall goal of the project was to elucidate how membrane dynamics influence the expression of genes, which are linked to pathological conditions. One prominent example in this respect are heat shock proteins (Hsps). So far, conventional biochemical techniques were used to study the machanisms of Hsp translocation to the membrane and its physical state in the membrane. However, these measurements are not capable to study membrane dynamics in detail in living cells. By contrast, single molecule techniques like single dye tracing (SDT) enable direct observation of the movement of individual molecules in cellular membranes. 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.
Data: CORDIS, © European Union
Project objective
This project focuses on the elucidation of membranes as targets of stress signalling. Stress signalling plays a crucial role in chronic disorders like diabetes mellitus, heart disease, kidney failure or neuro-degenerative disorders. We will improve the understanding of the molecular basis of the diseases by applying a new imaging technology to study the membrane dynamic processes. The new technique permits the visualisation of single molecules and will be applied to investigate the level and cellular localisation of e.g heat shock proteins and to observe lipid- and protein-specific membrane domains and rafts engaged in HSP-signalling. An immediate outcome of the proposed research will be a better understanding of the molecular basis of the membrane-associated diseases. We also expect that the project will lead to the identification and characterization of new drug compounds, which rebalance the perturbed levels of HSP proteins in diseased tissue. Through the proposed project the host institutions Upper Austrian Research GmbH (UAR) and the Biological Research Center, Hungarian Academy of Sciences (BRC) will intensify their ongoing collaboration and combine their scientific strengths to improve the understanding of molecular basis of membrane-associated diseases. BRC is one of the leading scientific institutions working on stress-signalling of membranes and their involvement in diseases. UAR is a leading company in developing ultra sensitive fluorescence microscopes for single dye tracing (SDT) and HTS with single molecule sensitivity used for life science applications. The trade name of this tool is CytoScout. This integrated project follows a multidisciplinary approach and brings together experts from physics, chemistry, biology, molecular biology, clinical diagnostics, medicine and its scope ranges from basic science over applied research to clinical application.
Original text from CORDIS.
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Data: CORDIS, © European Union