ArticleProceedings of the National Academy of Sciences of the United States of America2015
Mechanistic links between cellular trade-offs, gene expression, and growth.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 203 papers.
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Who cites it
203 citing papers in PubMed.
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- On the conditions for shifts in metabolic strategies.PLoS computational biology · 2026Review
- Burden-aware feedback control of microbial consortia.Nature communications · 2026Article
- Suppression rather than activation of the integrated stress response (GCN2-ATF4) pathway extends lifespan in the fly.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- HySimODE: a hybrid stochastic-deterministic simulation framework for multiscale models of biological systems.Bioinformatics (Oxford, England) · 2026Article
- A synthetic ERFVII-dependent circuit in yeast sheds light on the regulation of early hypoxic responses of plants.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Synthetic Biology of Plants and Microbes for Agriculture, Environment, and Future Applications.Chemical reviews · 2026Review
- Quantitative Coarse-Grained Modeling of Microbial Metabolism: Uncovering Growth Laws, Environmental Responses, and Host-Circuit Coupling.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Article
- Maintenance of cytoplasmic and membrane densities shapes cellular geometry in Escherichia coli.Nature communications · 2025Article
- Programmable cell differentiation in budding yeast uncouples reproductive and metabolic tasks.bioRxiv : the preprint server for biology · 2025Article
- GBA Solver: a user-friendly web server for growth balance analysis.Bioinformatics (Oxford, England) · 2025Article
- Genetic controllers for enhancing the evolutionary longevity of synthetic gene circuits in bacteria.Nature communications · 2025Article
- CRISPRi-Linked Multimodule Negative Feedback Loops to Address Winner-Take-All Resource Competition.ACS synthetic biology · 2025Article
- Article
143 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intracellular processes rarely work in isolation but continually interact with the rest of the cell. In microbes, for example, we now know that gene expression across the whole genome typically changes with growth rate. The mechanisms driving such global regulation, however, are not well understood. Here we consider three trade-offs that, because of limitations in levels of cellular energy, free ribosomes, and proteins, are faced by all living cells and we construct a mechanistic model that comprises these trade-offs. Our model couples gene expression with growth rate and growth rate with a growing population of cells. We show that the model recovers Monod's law for the growth of microbes and two other empirical relationships connecting growth rate to the mass fraction of ribosomes. Further, we can explain growth-related effects in dosage compensation by paralogs and predict host-circuit interactions in synthetic biology. Simulating competitions between strains, we find that the regulation of metabolic pathways may have evolved not to match expression of enzymes to levels of extracellular substrates in changing environments but rather to balance a trade-off between exploiting one type of nutrient over another. Although coarse-grained, the trade-offs that the model embodies are fundamental, and, as such, our modeling framework has potentially wide application, including in both biotechnology and medicine.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.