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Comparative functional genomics of cellular signalling pathways

Objective

Cancer and many other human diseases are often caused by aberrations in cellular signalling pathways. Mutations in signalling genes have been shown to stimulate cell proliferation and migration, and ultimately leading to uncontrolled growth and metastasis. Such examples include Wnt, Hedgehog, Notch signalling pathways which are also required for proper development from invertebrates to mammals.

Signal transduction pathways are essential cellular processes in development and homeostasis for every complex organism. Studies in model organisms such as C. elegans, Drosophila and mice have contributed significantly to the understanding of how cells transmit information in vivo. We have previously shown that Wnt pathways in human and Drosophila cells lead to the activation of distinct intracellular signalling routes that control cell specification, proliferation and migration. Specifically, we propose here to use cellular assays and genome-wide RNAi to systematically identify components of signalling pathways both in human cells and Drosophila cells.

During the past years, we have developed methodologies to perform rapid high-throughput RNA interference screens in cell-based assays. We will use a comparative functional genomics approach that will allow us to use the advantages of a less complex invertebrate genome to comprehensively identify genes that may be missed in our parallel approaches in human cells. Identified pathway components will be further characterized using genetics, biochemical and molecular methods and will be analysed for deregulation in human cancers. These components constitute targets for drug discovery to interfere with inappropriate signalling pathway activation during disease.

We envision building a team that is highly competitive at the forefront of international research, to train and retain scientists in Europe and develop an experimental platform for rapid functional annotation of the genome and to enable treatments for human diseases.

Call for proposal

FP6-2002-MOBILITY-8
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Coordinator

DEUTSCHES KREBSFORSCHUNGSZENTRUM
Address
Im Neuenheimer Feld 280
Heidelberg
Germany

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