We discuss three examples of NMR-based metabolomics in model organisms: Unravelling central metabolic regulation in C. elegans, and exploring host-symbiont interactions between Wolbachia and Drosophila melanogaster and Aedes aegypti :
(1) Previously we discovered that the enzyme dihydrolipoamide dehydrogenase (DLD) causes phosphine resistance in C. elegans and is likely a metabolic master regulator [1]. Genome-scale metabolic models (GSMs) are key tools to understanding metabolism and the role of DLD in C. elegans, and we are now leading the international research consortium WormJam which aims to curate a C. elegans consensus GSM [2-3].
(2) Wolbachia infection in D. melanogaster depresses the insulin/insulin-like-growth factor cascade, whilst inducing the hypoxia signaling pathway [4]. This causes ROS production and ROS adaptations, and other metabolic changes that steer metabolism away from oxygen-intensive pathways and enable metabolite extraction by the symbiont and metabolite provisioning to the host. These responses signify a reprogramming of the host’s mitochondrial metabolism rather than an immune response.
(3) In contrast, infection with wMelPop in Ae. aegypti triggers host immune responses, including melanogenesis and ROS production. wMelPop is more aggressive, while wMel is more likely to form stable inheritable infections.
These examples show the breadth and depth of insights that can be gained through model organisms in metabolomics and systems biology.