SpoT–RelA regulatory logic and physiology under perturbed (p)ppGpp
Clarify the regulatory logic of SpoT and its interplay with RelA in (p)ppGpp control, and establish a comprehensive understanding of cellular physiology under perturbed (p)ppGpp conditions, including the validity of ppGpp homeostasis assumptions.
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On the modeling front, the recent advances connecting ppGpp dynamics to translation elongation in E.~coli demonstrate the power of hybrid approaches to bridge the power of coarse-grained models with the specific predictions of mechanistic descriptions. However, several open questions remain, such as the regulatory logic of SpoT and its interplay with RelA, and a full understanding of the physiology under perturbed ppGpp conditions, challenging long-standing assumptions about ppGpp homeostasis.