Objective
In recent years, the zebrafish has emerged as a new vertebrate model organism for biomedical research which offers a unique combination of traits: a short generation time, small size and efficient breeding procedures make it the best choice among vertebrates for forward genetic screening and small-molecule screens, including toxicology, while the transparent embryo and larva offers unique opportunities for imaging of cell movement and gene expression in a developing organism. Building on recent advances in the zebrafish field, we will conduct high-throughput phenotyping of at least a thousand regulatory genes relevant for common human diseases, by behavioural assays (for viable mutants), 3D / 4D imaging and expression profiling (including high-throughput sequencing). We will include mutants generated by TILLING and by the new zinc finger nuclease method, as well as mutants from earlier forward-genetics screens. A phenotyping effort of this scale has never been undertaken before in any vertebrate organism. Complementing the study of mutants relevant for neurological disorders, we will produce an atlas of gene expression in the brain, the most comprehensive one in a vertebrate. We will further perform a genome-wide characterisation of regulatory elements of potential disease genes by a combination of bioinformatics and transgenics. Small-molecule screening for mutant rescue or disease-relevant processes will identify candidate drugs and provide insights into gene function. Our increasing knowledge on the regulators and their interactions with regulatory targets will be integrated with knowledge at cellular and organismic level. By capitalising on the virtues of the zebrafish system, this systems biology approach to the regulome will gain unique knowledge complementing ongoing work in mammalian systems, and provide important new stimuli for biomedical research.
Fields of science
Call for proposal
FP7-HEALTH-2009-two-stage
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Funding Scheme
CP-IP - Large-scale integrating projectCoordinator
76131 Karlsruhe
Germany
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Participants (19)
79098 Freiburg
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75794 Paris
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CB10 1SA SAFFRON WALDEN
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1011 JV AMSTERDAM
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75654 Paris
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WC2R 2LS London
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2311 EZ Leiden
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80539 Munchen
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01069 Dresden
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S10 2TN Sheffield
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35122 Padova
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50931 Koln
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8006 Zurich
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WC1E 6BT London
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Participation ended
5008 BERGEN
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B15 2TT Birmingham
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2006 Sydney
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28760 Tres Cantos
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SW7 2AZ LONDON
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