Uncovering and resolving challenges of quantitative modeling in a simplified community of interacting cells

PLoS Biology
Samuel F M HartWenying Shou

Abstract

Quantitative modeling is useful for predicting behaviors of a system and for rationally constructing or modifying the system. The predictive power of a model relies on accurate quantification of model parameters. Here, we illustrate challenges in parameter quantification and offer means to overcome these challenges, using a case example in which we quantitatively predict the growth rate of a cooperative community. Specifically, the community consists of two Saccharomyces cerevisiae strains, each engineered to release a metabolite required and consumed by its partner. The initial model, employing parameters measured in batch monocultures with zero or excess metabolite, failed to quantitatively predict experimental results. To resolve the model-experiment discrepancy, we chemically identified the correct exchanged metabolites, but this did not improve model performance. We then remeasured strain phenotypes in chemostats mimicking the metabolite-limited community environments, while mitigating or incorporating effects of rapid evolution. Almost all phenotypes we measured, including death rate, metabolite release rate, and the amount of metabolite consumed per cell birth, varied significantly with the metabolite environment. Once w...Continue Reading

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Citations

Jun 13, 2019·FEMS Microbiology Letters·Alan R Pacheco, Daniel Segrè
May 6, 2019·Nature Communications·Lori NiehausBabak Momeni
Jun 18, 2020·MSystems·Jai A Denton, Chaitanya S Gokhale
Jun 30, 2019·The ISME Journal·Alex CarrSean M Gibbons
Jan 18, 2020·Nature Communications·Feng LiuTing Lu
May 23, 2021·FEMS Microbiology Ecology·Erik S WrightKalin H Vetsigian
Jun 8, 2021·Current Opinion in Microbiology·Yili QianOphelia S Venturelli
Aug 7, 2019·ACS Synthetic Biology·Feng LiuQiang Hua

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Methods Mentioned

BETA
flow cytometry
genetic modifications
fluorescence imaging
fluorescence microscopy

Software Mentioned

GATK
FlowJo
Perl
Sim
Bioact
LabVIEW
CoSMO
IGV
vcftools
custom Perl script

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