FlySilico: Flux balance modeling of Drosophila larval growth and resource allocation

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.

The Metabolic Response to Infection With Wolbachia Implicates the Insulin/Insulin-Like-Growth Factor and Hypoxia Signaling Pathways in Drosophila melanogaster

“…In this context, it would also be intriguing to further explore the hypothesis that Wolbachia produces riboflavin for the Drosophila host cells, by designing fluxomics experiments that target specifically the fate of riboflavin. The metabolic interactions between Wolbachia and Drosophila also lend themselves to exploration via genome-scale modeling using available genome-scale metabolic models for both organisms (Coquin et al, 2008;Jiménez et al, 2019;Schönborn et al, 2019).…”

Modeling Drosophila gut microbe interactions reveals metabolic interconnectivity

“…Thus, growth of the bacteria on HD was particularly important, as this diet allows the exact description of the input for the modeling experiments. In the past, we already benefitted from this for modeling the growth and metabolism of Drosophila larvae ( Schönborn et al., 2019 ). In order to reconstruct the genome-scale metabolic networks of the isolated bacteria, our next step was to sequence their respective genomes using the Illumina MiSeq platform (see material and methods).…”

A Personalized Therapeutics Approach Using an In Silico Drosophila Patient Model Reveals Optimal Chemo- and Targeted Therapy Combinations for Colorectal Cancer

“…Several network models of biomolecular regulation in Drosophila have been reported for investigating the regulatory dynamics in cancer (90,91,(112)(113)(114). Specifically, such applications of adult Drosophila midgut models are particularly useful in investigating CRC due to cellular and organizational similarities between Drosophila midgut and the human colon.…”