Research Institute of Molecular Pathology (IMP).
In higher eukaryotes, genes are expressed dynamically in complex spatial and temporal patterns, which are progressively refined to set up body plans and define specific cell-types. The information about when and where each gene is to be expressed is encoded in the sequences of promoter- and enhancer regions and realized by transcription factor and cofactor proteins.
I am presenting our work towards understanding how this regulatory information is sequence-encoded and how cells utilize this information with transcription factor and cofactor proteins. We functionally characterize regulatory sequences by enhancer screens in Drosophila S2 cells and by a genome-scale candidate testing approach in developing Drosophila embryos. We then use deep-learning approaches to model the sequence-to-function relationship for S2 cell type-specific enhancers quantitatively and for different target tissues in the Drosophila embryo in vivo. We investigate the learned sequence- and grammar rules, e.g. relating to motifs, motif flanks and motif-motif distances, and build synthetic enhancers de novo.