Bridging the gap: Unravelling the interaction between metabolism and signalling in health and disease

To unravel the interaction between metabolic networks, signal transduction and gene regulation and thus the impact of nutrition on health and disease is a major challenge of current life science research. Two major metabolic pathways have been recently id entified which potentially link metabolism to signal transduction and gene regulation. One is the tryptophan pathway, specifically, its kynurenine branch. The other is NAD-metabolism, including both NAD-biosynthesis and -consumption. These two pathways ar e tightly connected to signalling networks. In particular, the mammalian target of rapamycin(mTOR)-pathway, the major nutrient sensing signalling pathway in humans, and the aryl hydrocarbon receptor (AHR) pathway (important e.g. for immune suppression in the context of tumor development) stand out. Changes in tryptophan and NAD-metabolism are known to affect posttranslational modifications of proteins (e.g. histone methylation and acetylation) and thereby have profound impact on gene expression. It is the refore not surprising that changes in NAD- and tryptophan metabolism as well as mTOR- and AHR-dependent signalling are relevant for a large number of diseases. However, the molecular mechanisms of the cross-regulation and mutual interactions of these path ways have remained largely unknown. Therefore, the primary goal of the research exchange proposed here is to bring together experts from these different fields to foster interdisciplinary training and mutual understanding and bridge the existing gap betwe en research on metabolic pathways and signal transduction. Given the complexity of the biological processes involved and the high interconnectivity between the pathways, a systems biology approach forms the core of the proposed research exchange. Moreover , mutual training of researchers from the individual experimental and the biomathematical modelling groups are envisaged.