Radoslaw Ejsmont - CRI Research Fellow
Drosophila melanogaster, a popular model organism to study animal development currently lacks a comprehensive set of synthetic biology tools. Such a toolkit would enable in vivo modeling of biological pathways that control developmental processes. I will present projects, currently running in my team, that address these issues. We are working on a synthetic transcription factor framework, based on TAL effectors and a variety of activation and repression domains. We will use these factors to recapitulate gene regulatory motifs that commonly occur in developmental gene regulatory networks as well as create computation units that perform basic logical binary operations. The synthetic transcription factor framework will enable in vivo modeling of gene regulatory circuits that control cell differentiation and other developmental processes. To elucidate which members of developmental networks are essential for their function, we are developing a massively-parallel CRISPR-based synthetic rescue screen strategy. To enable the integration of synthetic transcription factors with the host pathways, we are working on strategies for the replacement of native transcription factors with their synthetic counterparts and for simultaneous insertion of multiple synthetic transcription factor binding sites upstream of the host target genes. Finally, we are using metabolic engineering to create new evolvable and selectable traits. We will use these tools to study two developmental events in Drosophila: the specification of photoreceptor neurons in the retina and the establishment of segmentation patterns in embryo development.