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Next-Generation Microscopy with Pharmacoscopy

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A novel microscopy method, developed and patented by scientists from CeMM, allows unprecedented insights into the spatial organization and direct interactions of immune cells within blood and other liquid multi-lineage tissues. The assay, called Pharmacoscopy and published in Nature Chemical Biology, is able to determine the immunomodulatory properties of drugs within large libraries on immune cells in high resolution and high throughput. 

The search for new drugs, small molecule or biologicals, that influence the immune system in a desired manner is challenging: immune signaling, often a combination of communication via soluble proteins and direct interaction by cell-cell contacts, is subtle and hard to track in all its nuances. So far, there has been a lack of fast and robust technology to measure the effect of a potential immunomodulatory drug in particular in a cell-cell contact dimension. 

By combining state-of-the-art high-throughput fluorescent microscopy with single cell image analysis and novel analysis algorithms, Pharmacoscopy provides a powerful solution. Developed by a group of scientists at CeMM led by Director Giulio Superti-Furga and tested in collaboration with the Medical University of Vienna, Pharmacoscopy can quantify the overall spatial patterning and direct interactions of immune cells within blood with unprecedented speed and accuracy. The method was introduced in Nature Chemical Biology (DOI:10.1038/nchembio.2360).

Combined single cell resolution and fully automated platform control, Pharmacoscopy can test large drug libraries, as available in Stefan Kubicek’s PLACEBO (Platform Austria for Chemical Biology) laboratory, for compounds with immunomodulatory potential. With this method, the scientists identified Crizotinib, an FDA approved drug for non-small cell lung cancer, to have a previously unknown immunomodulatory potential.

Publication:

Gregory I. Vladimer, Berend Snijder, Nikolaus Krall, Johannes W. Bigenzahn, Kilian V.M. Huber, Charles-Hugues Lardeau, Kumar Sanjiv, Anna Ringler, Ulrika Warpman Berglund, Monika Sabler, Oscar Lopez de la Fuente, Paul Knöbl, Stefan Kubicek, Thomas Helleday, Ulrich Jäger, and Giulio Superti-Furga. Global survey of the immunomodulatory potential of common drugs. Nature Chemical Biology, April 24, 2016. DOI:10.1038/nchembio.2360

Funding: 

This study was supported by the European Research Council, the Austrian Science Fund (FWF), Swiss National Science Foundation, European Molecular Biological Organization, the Austrian Federal Ministry of Science, Research and Economy, The National Foundation for Research, Technology and Development, The Swedish Cancer Society, the Kunt and Alice Wallenberg Foundation, the Torsten and Ragnar Söderberg Foundation, and the Marie-Sklodowska Curie Fellowships.