Gene regulatory and metabolic network structure, function and evolution

PROJECT SUMMARY Metabolism and gene expression lie at the heart of most, if not all, biological processes and both can go awry in a plethora of human diseases. Metabolic changes affect gene expression and vice versa. While the interplay between metabolism and gene expression has been studied at the level of individual genes and pathways, many questions remain unexplored, especially at the systems, or network, level. The central question underlying this proposal is: How, where and why does transcription control metabolism and vice versa? Several key questions and challenges pertaining to this overarching question will be addressed using the nematode C. elegans as a whole animal model system. We will employ genetic screens, gene expression profiling and metabolomics to answer key questions at different levels of resolution: from the network level, to the pathway level, the circuitry/molecular level. This enables us gain both broad, systems-level as well as deep mechanistic insights into the metabolic control of gene expression and the transcriptional control of metabolism.