Large-scale RNAi screens add both clarity and complexity to Drosophila NF-κB signaling.

NF-κB signaling is an immune response mechanism remarkably conserved through phylogeny. The genetically tractable model animal Drosophila melanogaster is an important model organism for studying NF-κB signaling in the immune response. Fruit flies have two NF-κB signaling pathways: the Toll and the Imd pathway. Traditional genetic screens have revealed many important aspects about the regulation of Drosophila NF-κB signaling and have helped us to also understand the immune response in humans. For example, the discovery that Toll like receptors are the main immune signaling molecules in mammals was based on work in flies. During the past decade high throughput RNA interference (RNAi)-based screening in cultured Drosophila cells has become a common method for identifying novel genes required for numerous cellular processes including NF-κB signaling. These screens have identified many novel positive and negative regulators of Drosophila NF-κB signaling thus enhancing our understanding of these signaling cascades.