ZF-HEALTH

Zebrafish regulomics for human health

Activity Code: HEALTH-2009-2.1.1-1
Coordinator: Karlsruhe Institute of Technology (KIT)

 

Abstract:

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 trans-genics. 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.

 

Project Details:

Start Date:  01.07.2010
End Date: 31.12.2015
EU Contribution:  11.38 Mio. Euro
Total Costs: 14.96 Mio. Euro
Funding Scheme: Large-scale integrating project
Contact Person: Natascha Wallburg, natascha.wallburg(at)kit.edu

 

Partners:

  • Karlsruhe Institute of Technology, Germany
  • Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., München, Germany
  • Genome Research Ltd, Cambridge, United Kingdom
  • University College London, United Kingdom
  • Institut National de la Santé et de la Recherche Médicale (INSERM), France
  • Albert-Ludwigs-Universität Freiburg, Germany
  • Universita' degli Studi di Padova, Italy
  • Leiden University, Netherlands
  • Universität Zürich, Switzerland
  • The University of Birmingham, United Kingdom
  • ZF Biolabs SL, Spain
  • Uni Research AS, Norway
  • Koninklijke Nederlandse Akademie van Wetenschappen, Netherlands
  • Technische Universität Dresden, Germany
  • Universität zu Köln, Germany
  • Centre National de la Recherche Scientifique (CNRS), France
  • The University of Sheffield, United Kingdom
  • King's College London, United Kingdom
  • The University of Sydney, Australia
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