Creating balance: Resource allocation in E.coli

To grow and survive, bacteria need to allocate their precious nutrients wisely. A big challenge they face is to balance the synthesis of ribosomes, the machinery that produces proteins, and proteins themselves. Previous studies found that ribosome levels are tightly coupled to growth rate, and proposed that this linear relationship reflects an optimal allocation strategy. However, my work on E.coli growth under nutrient limitations shows that under slow growth conditions, cells use several strategies to achieve the same protein synthesis rate. By combining mathematical modeling and experimental measurements including ribosome profiling, I show how cells tune various aspects of translation. Under phosphate (P) limitation, translation is slow due to a particularly low abundance of ribosomes, which are RNA-rich and thus particularly costly for phosphorous-limited cells. In nitrogen (N) limited conditions, translational elongation is slowed by processes including ribosome stalling at glutamine codons. Under carbon (C) limitation, translation is slowed by the accumulation of inactive ribosomes not bound to mRNA. I have also found that the extra ribosomes accumulated in C- and N-limited cells accelerate growth when nutrients reappear. Taken together, these results shed light on the global regulation of bacterial translation and the trade-off between maximizing growth and being prepared to rapidly adapt if nutrient availability changes.