The identification of novel components of the Drosophila JAK/STAT pathway

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The JAK/STAT signal transduction pathway has been conserved throughout evolution and has been implicated in some leukemias and developmental events including haematopoiesis. As a result considerable work has been undertaken in vitro and in tissue culture systems to characterise the components and functions of the pathway. However no genetically based approach to identifying pathway components has yet been undertaken. I therefore propose to undertake a systematic genetic screen to isolate genes which interact with the JAK/STAT pathway conserved in Drosophila. I have developed a Drosophila stock that over-expresses the fly JAK/STAT pathway ligand in the eye and results in cellular over-proliferation. This proliferation produces a massive overgrowth and enlargement of the adult eye that is both easily visible in a binocular microscope and dependent on signalling by the downstream pathway components. Initial results indicate that the screen is feasible and have defined genomic regions that contain interacting genes. A small scale pre-screen has identified a number of genes that appear to be involved in JAK/STAT signalling. Two of these contain P-element insertions and represent a homologue of a known tumour suppresser and a zinc finger protein. Follow up investigations into the function of genes identified by the screen will be undertaken and their role in JAK/STAT signalling and development will be analysed. In the long term, it is hoped to be able to identify novel components of the JAK/STAT signalling pathway and understand the mechanisms that regulate its activity.