Collaborative Research: Living on the Edge - Quantitative Systems Physiology of Iron Homeostasis

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This project will delineate how BRUTUS (BTS), an iron-binding protein confined to the plant vasculature, controls iron (Fe) handling throughout the plant – dynamically responding to changes in Fe levels by regulating other proteins that are able to move through the plant root and shoot. As in mammals, Fe is a critical nutrient and essential for several cellular processes. Unfortunately, it is also potentially toxic to cells. Thus, cells must tightly regulate Fe availability. By revealing how BTS acts as a master regulator of Fe status in plants, this work will provide new molecular targets for generating crops with increased nutrient content or tolerance to pervasive alkaline soils, in which Fe is poorly available. Over the course of this project, the investigators will collaborate with NC and TN 4-H Youth Development programs to create experiential learning modules for youth in rural and minority communities to gain awareness of plant biology fundamentals through activities designed to promote systems thinking.E3 ubiquitin ligases are central to Fe homeostasis in both mammals and plants. In the model plant Arabidopsis thaliana, the absence of the iron-binding ubiquitin ligase, BRUTUS (BTS), leads to systemic Fe excess. Although it causes the degradation of transcription factors that promote Fe uptake, BTS and its transcription factor targets are both transcriptionally upregulated in response to Fe deficiency. It is unclear how the concurrent activation of Fe response activators and their antagonists resolves systemic deficiency. The long-term goal of this project is to delineate the molecular rules underlying systemic Fe homeostasis in Arabidopsis. Guided by iteratively refined, model-derived hypotheses, a combination of molecular biology, imaging, biochemical, and systems biology approaches will be used to 1) characterize the molecular and intracellular dynamics of BTS and its targets in the root in response to Fe availability, 2) determine the role of oligomerization in regulating mobility and activity of deficiency responsive transcription factors, and 3) identify a shoot-specific network motif that allows BTS to act as a sensor that is both responsive to and responsible for the regulation of systemic Fe deficiency signals. The proposed work will provide new perspectives on how nutrient sensing in a multicellular organism orchestrates changes in protein-protein interactions in a tissue- and cell-specific manner and demonstrate how the details of a complex, multiscale regulatory phenomenon can be uncovered more efficiently by adopting a model-driven research strategy.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.