Western societies are faced with a variety of human conditions of neurological nature spanning from cancer to psychological disorders. In biomedical research Drosophila has been used extensively as a genetic model organism to study development and disease related phenotypes. Many key molecules that participate in the development of the nervous system are conserved from fly to human. Here, I propose to combine the powerful Drosophila genetics with the novel deep-sequencing assays to reveal what determines the neural stem cell (neuroblast) fate in the developing embryo. In particular, I propose to map the genome binding events of co-operating key gene regulatory transcription factors specifically in the early neuroectoderm from which nascent neuroblasts will arise. I will also document the chromatin structure and gene expression profiles in these two distinct tissues, neuroectoderm and neuroblasts. This systems biology approach will reveal what determines neural stem cell biogenesis at the global genomic level, which remains to date unexplored. Drosophila is ideal for this approach, as it affords sophisticated transgenesis tools for the targeting of bait molecules to specific tissues and developmental stages. In addition, I aim to integrate our Drosophila data with available expression data form human neural tissue diseases in order to discover potential novel candidates relevant for human disease by cross-species bioinformatics. The successful completion of this proposal will be the cornerstone in my career development path establishing me as a competitive independent researcher in the field of transcriptional regulation of complex multicellular systems.
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