The gastrointestinal tract is emerging as a key regulator of appetite and metabolism, but studies aimed at identifying the signals involved are faced with daunting neuroanatomical complexity: there are as many as 500 million neurons in the human gut. Drosophila should provide a simple and genetically amenable alternative, but both its autonomic nervous system and the signalling significance of its digestive tract have remained largely unexplored. My research programme will characterize the signals and neurons mediating the interaction between the nervous and digestive systems, and will establish their significance both in the maintenance of metabolic homeostasis and in response to nutritional challenges. To achieve these goals, we will capitalize on a multi-disciplinary approach that combines the genetic manipulation of defined neuronal lineages, a cell-biological approach to the study of enterocyte metabolism, and our recently developed physiological and behavioural readouts. Our work will provide new insights into the signals and mechanisms modulating internal metabolism and food intake: processes which, when deregulated, contribute to increasingly prevalent conditions such as diabetes, metabolic syndrome and obesity. Our recent finding of conserved mechanisms of autonomic control in the fruit fly makes us confident that the signals we identify will be relevant to mammalian systems.