Objective The Notch (N) signaling pathway is conserved throughout the animal kingdom and is widely used during development for many cell fate and cell proliferation decisions. In particular, Notch is involved in controlling the number of neurons in both vertebrates and invertebrates, and it has also been linked to several human cancers. Despite the widespread use of this signaling pathway, very few target genes are currently known.The aim of this proposal is to identify new target genes of the N pathway. We will use the fruit fly Drosophila melanogaster as a model system, because phenotypes associated with activation or inhibition of N are very well characterized, and it allows the use of genetics to study the function and interaction of the new genes. Potential N tar get genes will be identified by DNA micro-array analysis using RNA from Drosophila cell lines or larval imaginal discs cells expressing an activated form of the N receptor. Comparing databases obtained from these different scenarios will allow us to identi fy the putative primary target genes of N signaling. These genes will be further analyzed in vivo for their relevance in the N pathway using the classical genetic tools available in the fly. Then, their function will be assessed using biochemical, molecula r and cellular studies. Our work will focus primarily on those genes for which mutants and antibodies are already available.The identification of such N target genes is of enormous interest given the recurrent use of this pathway throughout development and during normal physiology of many tissues. Furthermore, since drugs directed against core components of the N pathway are very likely to have numerous side effects, these new downstream effectors, accounting for only one part of the N response, might repre sent in this respect better drug targets. Fields of science natural sciencescomputer and information sciencesdata sciencedata miningmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicinephysiologynatural sciencesbiological scienceszoologymammalogynatural sciencesbiological scienceszoologyinvertebrate zoology Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Topic(s) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Call for proposal FP6-2004-MOBILITY-5 See other projects for this call Funding Scheme EIF - Marie Curie actions-Intra-European Fellowships Coordinator CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE EU contribution No data Address Trinity LaneThe Old Schools CAMBRIDGE United Kingdom See on map Links Website Opens in new window Total cost No data
