RNAi technology can also be used in a combinatorial fashion to knock down the activity of two or more genes at a time, which permits detection of genes acting in parallel in a given process or pathogenic infection. In one study, Dorer and colleagues performed Host-pathogen interactions in Drosophila PERSPECTIVE a series of single and double gene knockdown experiments of 73 genes in Kc cells to test the hypothesis that Legionella pneumophila, the agent of Legionnaires' disease, recruits membrane material from endoplasmic reticulum (ER)-to-Golgi trafficking (Dorer et al., 2006) . Although few single knockdowns had much of an effect, the authors found evidence supporting their hypothesis in several double knockdown experiments. For example, double knockdown of the intermediate compartment and Golgi-tethering factor transport protein particle (TRAPP) together with the ER SNARE protein Sec22 resulted in reduced pathogen replication efficiency. They also showed a requirement in bacterial replication for the Cdc48-p97 complex that is involved in ER-associated degradation, and demonstrated that this complex is also important for Legionella pneumophila replication in mouse bone-marrow-derived macrophages. These studies underscore the role of endocytosis in phagocytic host cells and, owing to the combinatorial power of the system used, revealed a role for endocytic steps carried out by parallel mechanisms.