ZF-Tools - Molecular Cell Biology
- High-throughput Tools for Biomedical Screens in Zebrafish
“ZF-TOOLS - High-throughput Tools for Biomedical Screens in Zebrafish ” is a Specific Targeted Research Project funded by the European Commission as part of its Sixth Framework Programme (EC Contract LSHG-CT-2006-037220). The duration of the project was from January 2007 until June 2010.
The ZF-TOOLS project was a coordinated effort of three research laboratories and three SMEs aimed at the following objectives:
1. Genomic-based marker discovery for biomedical screens in zebrafish.
2. Use of high-throughput marker analysis and tumor cell implants for the identification of tumor growth and metastasis factors and organismal defense factors.
ZF-TOOLS aimed to develop a case study for an anti-tumor drug screening system, based on implantation of fluorescently labeled tumor cells into zebrafish embryos. The optically transparent embryos provide a highly useful in vivo system to monitor growth and metastasis of implanted tumor cells. The screening system allows for the powerful combination of visual monitoring with high-throughput analysis of expression of marker genes with a predictive value for tumor progression or for defense responses towards developing tumors. A multidisciplinary functional genomics approach was undertaken to discover relevant marker sets for biomedical screens in zebrafish.
- Zebrafish Model
No other vertebrate model organism’s popularity has grown as quickly as that of the zebrafish. The reputation of this small tropical fish was firmly established during the nineties when two big genetic screening projects in the US and Europe led to the discovery of hundreds of mutants that gave novel insights into the functions of essential developmental genes. These and other genetic studies confirmed that the zebrafish is a good predictive model for human development. The second reason for the rapid expanse of zebrafish colonies in research labs is the optical transparency of the zebrafish embryos. This property makes them ideally suited for microscopical imaging of life processes. European funding of the ZF-MODELS project has contributed enormously to the creation of common resources for the zebrafish community, such as libraries of knock-out mutants and collections of transgenic fish. The success of ZF-MODELS has paved the way for two new European projects, ZF-TOOLS and ZF-CANCER, both coordinated by Leiden University. For further information on the use of zebrafish for biomedical research we refer to the European network on Fish Biomedical Models (EUFishBioMed).
Although the zebrafish embryo has great potential for application in high-throughput drug discovery screens, the development of such screening systems is limited by knowledge of disease-related marker genes in zebrafish. In the ZF-TOOLS project we have used different genomics approaches, including novel deep sequencing technology, to discover novel marker genes for cancer and immunity in zebrafish. Based on the genomics results, we established convenient assays to analyze defined subset of relevant markers in a high-throughput manner. Three biotech enterprises will commercially exploit the expertise on bioinformatics, high-throughput genomics analysis, and high-throughput drug screening that was gained in the ZF-TOOLS project.
Dr.Annemarie H.Meijer ( coordinator ), Institute of Biology, Leiden University Leiden, The Netherlands
Prof.Dr. Herman P. Spaink, ZF-screens B.V. Leiden, The Netherlands
Dr. Nicholas Foulkes , Forschungszentrum Karlsruhe, Karlsruhe, Germany
Bas Reichert, BaseClear B.V. Leiden, The Netherlands
Dr. Tamás Forrai, Zenon Bio Ltd. Szeged, Hungary
Dr. Mátyás Mink , Szeged University Szeged, Hungary
- Download project brochure (right-click save as…)”
- Download Publishable Final Activity Report (right-click save as..)
Trede N, Meijer AH, Snaar-Jagalska BE, Spaink HP (2007) Model systems for infectious disease and cancer in zebrafish: a report on an EMBO workshop held at the Lorentz Center, Leiden, The Netherlands, July 16-18, 2007. Zebrafish. 4:287-92.
Schaaf MJM, Champagne D, van Laanen IHC, van Wijk DCWA, Meijer AH, Meijer OC, Spaink HP, Richardson MK (2008) Discovery of a functional glucocorticoid receptor β-isoform in zebrafish. Endrocinology, 149:1591-9
Brittijn SA, Duivesteijn SJ, Bitter W, de Bruin J, Champagne D, Cuppen E, Flik G, Janssen R, de Jong IM, de Kloet R, Kros A , Meijer AH, van der Sar AM, Schaaf MJM, Schulte-Merker S, Spaink HP, Tak PP, Vandenbroucke-Grauls CM, Vervoordeldonk MJ, Vonk FF, Witte F, Richardson MK (2009) Zebrafish Developmental Patterning: New Tools for Medical Research. Int J Dev Biol. 53:835-50
Stockhammer OW, Zakrzewska A, Hegedûs Z, Spaink HP, Meijer AH (2009) Transcriptome profiling and functional analyses of the zebrafish embryonic innate immune response to Salmonella infection. J Immunol. 182: 5641-53