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Regulation of Inflammation

Objective

Despite its fundamental importance, our understanding of the immediate mechanisms directing tissue response and the complex cell-cell communications regulating its resolution remain fairly limited. Moreover, current anti-inflammatory drugs work relatively unspecific as on-off switches, thereby exhibiting considerable side effects. Studies on innate immunity have benefitted from the introduction of the transparent zebrafish larvae as an assay system. Transgenic fish expressing fluorescent proteins in leukocytes allow direct quantification of the inflammatory response in real-time in a live animal. However, the assays used to date require physical wounding of the fish preventing even a medium throughput experimental scale. We have developed a novel wounding assay without the need for mechanical wounding allowing high throughput large-scale analyses towards a comprehensive understanding of inflammation.
Here, I propose the generation of an automated screening platform based on our specific ‘non-invasive’ chemical wounding followed by automated microscopy and image acquisition that will allow the in vivo screening of thousands of compounds in a matter of days with respect to their effect on leukocyte recruitment, leukocyte function, resolution of the response and general toxicity in a single assay; target profiling of small molecule ‘hits’ from by chemical proteomics and integration of acquired data into an interactive web-based repository aiming at an interconnected view of molecular networks guiding an innate immune response.
This platform will allow chemical and genetic screens to the identification of new molecular pathways involved in innate immunity. At the same time, our approach will identify lead compounds for the development of novel immuno-modulatory drugs with enhanced specificity allowing fine-tuning of inflammation by targeting particular aspects of an innate immune response.

Call for proposal

FP7-PEOPLE-2010-RG
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Coordinator

KARLSRUHER INSTITUT FUER TECHNOLOGIE
Address
Kaiserstrasse 12
76131 Karlsruhe
Germany

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Region
Baden-Württemberg Karlsruhe Karlsruhe, Stadtkreis
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Natascha Wallburg (Ms.)
Links
EU contribution
No data