Dissecting epigenetic signatures and cellular plasticity of Drosophila blood cells

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Physiological and pathological stimuli can induce cells to change their identity, a process referred to as transdifferentiation. We will use Drosophila blood cells as a model to dissect the molecular mechanisms underlying transdifferentiation. Larvae respond to insults such as wasp infection by a change of plasmatocyte into lamellocyte identity. Remarkably, lamellocytes appear after only eight hours. This rapid transdifferentiation involves dramatic changes to cell morphology and function: whereas plasmatocytes are small, multi-purpose macrophage-like cells, lamellocytes are highly specialized, giant cells that seek out wasp eggs and contribute to their destruction. Our preliminary results implicate three novel players in the regulation of lamellocyte formation: the transcriptional regulator U-shaped (Ush), the Nucleosome Remodeling and Deacetylation (NuRD) complex and Casein Kinase 2 (CK2). In this project we will test the hypothesis that CK2-mediated phosphorylation of NuRD facilitates swift alterations of the epigenome and transcriptome allowing the rapid expression of proteins that drive dramatic changes of cell morphology, motility and phagocytotic activity. Towards this end, we will combine our complementary expertise in genome-wide studies, proteomic approaches, genetics and high-resolution microscopy. The strong evolutionary conservation of factors and mechanisms between Drosophila and man shaping the innate cellular immune system gives our study a broad biomedical relevance.