Signalling pathways play a crucial role in the development of multicellular organisms and in the homeostasis of adult tissues. Their activation, by specific molecules, in defined cells, induces a cascade of molecular events leading to cells growing and dividing, becoming more specialised or dying. Mutations in components of signalling pathways have been linked to developmental defects or diseases such as cancer.
For example, the conserved Wnt signalling pathway, known to be involved in the development of muticellular organisms like Drosophila and humans, has been linked to colon cancer. Decades of research in model organisms like Drosophila led to the identification of numerous factors implicated in signalling pathways. However they have failed to reveal all the factors involved.
For my post-doctoral training, I joined Michael Boutros laboratory at the German Cancer Research Center (Heidelberg, Germany). Our aim is to identify new components of signalling pathways. For this purpose, we have developed assays in Drosophila cultured cells that measure pathway activity while we interfere with the expression of genes using RNA interference (RNAi). We have libraries that allow us to test all genes encoded by the Drosophila genome for their involvement in a signalling pathway.
During my post-doctoral training financed by EMBO, I have contributed to the characterization of two new components of signalling pathways. Both were identified in large-scale screens in Drosophila cultured cells. The first, IAP2, is involved in Drosophila immune response, and is required in a pathway activated by bacteria such as E.coli. This signalling pathway is closely related to pathways involved in cell death in mammals. The second, Evi, is a factor required for the secretion of Wnts in human and Drosophila. Fly mutants for evi die at an early stage of their development. Evi is also required at later stages of fly development for the proper development of the wings.
