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German Cancer Research Center (DKFZ) and University of Heidelberg |
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Michael Boutros
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The Group of Dr. Michael Boutros is part of the Functional Genomics Programme at the German Cancer Research Center (DKFZ) in Heidelberg. Our group is interested in the systematic analysis of signaling transduction pathways that are essential for development and homeostasis in all higher organisms.
Communication among cells is one of the most crucial processes that control a broad spectrum of biological functions including immune responses, cell differentiation, proliferation, and death. Dysregulation of signaling pathways has many severe consequences, leading to developmental defects and aberrant proliferation of cells that can cause cancer.
During the past years, the sequencing of the human genome and the genomes of model organisms led to the discovery of several ten thousand genes, many with unknown functions. One of our main research aims is to develop and apply systematic reverse genetic screens by RNA interference to comprehensively characterize gene function on a genome-wide scale with a focus on conserved and disease-relevant signaling pathways.
Our Division is equipped to perform standardized high-throughput assays monitoring diverse cellular phenotypes induced by gene knockdown in Drosophila or human cultured cells. These assays include pathway reporter activity, cell viability, cell growth, morphology and gene expression profiles. We apply HTS techniques such as luminescence and cytometry measurements, high-content microscopy and expression profiling by deep sequencing.
HTS assays generate large datasets that need to be processed in order to identify specific hits. In collaborations we have developed technologies and data analysis tools suitable for standardized high-throughput screens in any cell-based system (web cellHTS package in Bioconductor/R). Currently we are developing software tools to analyze complex phenotypes acquired by automated microscopy. The publicly accessible phenotype database GenomRNAi developed in our Division integrates annotation of RNAi reagents and functional information obtained from large-scale RNAi experiments. For designing and evaluating dsRNA constructs (Drosophila and C. elegans) we developed the web tool E-RNAi. The tool can also be used for the design of enzymatically-digested long dsRNA (esiRNAs) for mammalian cells.
Links to computational tools:
For more information visit our homepage www.dkfz.de/signaling/ |
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Recent Publications
Boutros, M. and Ahringer, J. (2008). The art and design of genetic screens: RNA interference. Nature Rev. Genet., 9:554-566.
Steinbrink, S. and Boutros M. (2008). RNAi screening in cultured Drosophila cells. Methods Mol. Biol., 420:139-1353.
Horn T., Arziman Z., Berger J., Boutros M. (2007). GenomeRNAi: a database for cell-based RNAi phenotypes. Nucleic Acids Res., 35:D492.
Boutros M, Bras L, Huber W. (2006). Analysis of cell-based RNAi screens. Genome Biology. 7:R66.
Bartscherer, K., N. Pelte, D. Ingelfinger, and M. Boutros. (2006). Secretion of Wnt ligands requires Evi, a conserved transmembrane protein. Cell, 125:523-33
Gesellchen, V., D. Kuttenkeuler, M. Steckel, N. Pelte, and M. Boutros. (2005). An RNAi screen identified a Role for IAP2 in Innate Immune Response in Drosophila. View at EMBO reports.
Muller, P., D. Kuttenkeuler, V. Gesellchen, M. Zeidler, and M. Boutros. (2005). Identification of JAK/STAT signaling components by genome-wide RNAi. Nature 436:871-5.
Arziman, Z., T. Horn, M. Boutros. (2005). E-RNAi: A web application to design optimized RNAi constructs. Nucleic Acids Res. 33:W582-88.
Boutros M., A. Kiger, S. Armknecht, K. Kerr, M. Hild, B. Koch, S. Haas, Heidelberg FlyArray, R. Paro and N. Perrimon (2004). Genome-wide RNAi Analysis of Cell Growth and viability in Drosophila. Science 303:832-835.
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