Regulation of RNAi RNAi is one of a number of small ncRNA mediated processes in animals. We have recently shown that signalling mediated by the second messenger, IP3 regulates the strength of responses to exogenous RNAi in C. elegans. This is the first signalling pathway which has been shown to modulate RNAi in C. elegans. The novelty of this discovery is that it suggests a mechanism by which the physiological state of an animal and thus its environment can regulate the RNAi response. We now wish to dissect the mechanism of this action by indentifying further molecules involved in the process and pin-pointing the cells in which they act. By so doing we aim to link external and internal signals to RNAi. To do this we will use a range of molecular, cellular, genetic and transgenic techniques in combination with image analysis and the quantification of whole animal development, physiology and behaviour. In addition to answering fundamental questions about RNAi the results may suggest routes for improving the exploitation of RNAi in other systems.