Systems level analysis of animal metabolism by multicompartmental graph- and constraints-based modelling

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One goal of systems biology is to explain and predict how an organism works in terms of underlying processes (metabolism, gene expression patterns etc.). The purpose of this application is to design and construct systems-level models of metabolism in an animal comprising multiple organs with overlapping but appreciably different metabolic repertoires. Our core system is the pea aphid Acyrthosiphon pisum, which bears obligate intracellular bacteria Buchnera aphidicola in a specialized organ, the bacteriome. The bacteria and bacteriome are treated as metabolic compartments that interact with the gut, fat body (the principal insect organ of intermediary metabolism) and embryos (accounting for up to 75% of the total biomass of aphids) via the insect circulatory system. Our modelling, thereby, explores the integration of metabolic networks across multiple components comprising two distinct genomes within a single organism. We particularly address two challenges: (1) To develop new algorithms leading to a better understanding of the structure of metabolic networks, improved routes to explore the networks systematically for extracting functional information, and a grasp of how such networks have arisen. (2) To devise multi-compartment models, using flux balance analysis, to explore the metabolic organisation of animals. The modeling process follows a step-wise increase in complexity and realism of metabolic integration, building from our previous metabolic reconstruction of Buchnera. The final model seeks to define the fully interactive metabolic network comprising Buchnera-aphid interactions in maternal tissues and embryos. In parallel, our models will be made available for use by the wider community.