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Adaptive modulation of the global cellular growth state of unicellular organisms is crucial for their survival in fluctuating nutrient environments. Because these organisms must be able to respond reliably to ever varying and unpredictable nutritional conditions, their nutrient signaling networks must have a certain inbuilt robustness. In eukaryotes, such as the budding yeast Saccharomyces cerevisiae, distinct nutrient signals are relayed by specific plasma membrane receptors to signal transduction pathways that are interconnected in complex information-processing networks, which have been well characterized. However, the complexity of the signaling network confounds the interpretation of the overall regulatory “logic” of the control system. Here, we propose a literature-curated molecular mechanism of the integrated nutrient signaling network in budding yeast, focusing on early temporal responses to carbon and nitrogen signaling. We build a computational model of this network to reconcile literature-curated quantitative experimental data with our proposed molecular mechanism. We evaluate the robustness of our estimates of the model’s kinetic parameter values. We test the model by comparing predictions made in mutant strains with qualitative experimental observations made in the same strains. Finally, we use the model to predict nutrient-responsive transcription factor activities in a number of mutant strains undergoing complex nutrient shifts. 

The study of complex biological systems necessitates computational modeling approaches that are currently underutilized in plant biology. Many plant biologists have trouble identifying or adopting modeling methods to their research, particularly mechanistic mathematical modeling. Here we address challenges that limit the use of computational modeling methods, particularly mechanistic mathematical modeling. We divide computational modeling techniques into either pattern models (e.g., bioinformatics, machine learning, or morphology) or mechanistic mathematical models (e.g., biochemical reactions, biophysics, or population models), which both contribute to plant biology research at different scales to answer different research questions. We present arguments and recommendations for the increased adoption of modeling by plant biologists interested in incorporating more modeling into their research programs. As some researchers find math and quantitative methods to be an obstacle to modeling, we provide suggestions for easy-to-use tools for non-specialists and for collaboration with specialists. This may especially be the case for mechanistic mathematical modeling, and we spend some extra time discussing this. Through a more thorough appreciation and awareness of the power of different kinds of modeling in plant biology, we hope to facilitate interdisciplinary, transformative research.