Abstract
Organisms depend on a highly connected and regulated network of biochemical reactions fueling life sustaining and growth promoting functions. While details of this metabolic network are well established, knowledge of the superordinate regulatory design principles is limited. Here, we investigated by iterative wet lab and modeling experiments the resource allocation process during the larval development of Drosophila melanogaster. We chose this system, as survival of the animals depends on the successful allocation of their available resources to the conflicting processes of growth and storage metabolite deposition. First, we generated “FlySilico”, a curated metabolic network of Drosophila, and performed time-resolved growth and metabolite measurements with larvae raised on a holidic diet. Subsequently, we performed flux balance analysis simulations and tested the predictive power of our model by simulating the impact of diet alterations on growth and metabolism. Our predictions correctly identified the essential amino acids as growth limiting factor, and metabolic flux differences in agreement with our experimental data. Thus, we present a framework to study important questions of resource allocation in a multicellular organism including process priorization and optimality principles.
Highlights
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In order to model Drosophila larval growth and resource allocation, we first constructed a flux balance capable metabolic network covering the biochemical pathways necessary to metabolize the major constituents of the minimal, synthetic medium (Holidic diet; HD)[26], which we used to grow the fruit flies during the wet lab procedures
We decided to use a top-down modeling approach focusing on a generalized and averaged simple model of the growing larva, which we identified as a suitable system for Flux balance analyses (FBA) given its clear-cut objective function
Summary
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliat. We generated “FlySilico”, a curated metabolic network of Drosophila, and performed time-resolved growth and metabolite measurements with larvae raised on a holidic diet.
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