Iron (Fe) homeostasis is an exquisite example of biology’s ability to regulate the availability of nutrients that are simultaneously critical for basic processes of life and can act as potent cytotoxins. Fe plays a catalytic role in all primary metabolic processes. But, in excess, free Fe forms reactive oxygen species that cause the destruction of lipids, DNA, and proteins. Hence, Fe uptake, bioavailability, and localization must be tightly controlled in response to changing developmental and physiological needs. 

In this collaboration with Dr Terri Long at NC State University, Our research objective is to identify how BRUTUS, an iron-binding E3 ligase protein, choreographs systemic sensing and control of Fe status through its activity on mobile transcription factor targets. As the regulation of Fe status takes place at multiple levels (transcriptional and post-translational), and it involves cell-to-cell movement of regulatory proteins, we are using a mechanistic systems-modeling framework to integrate heterogeneous data, iteratively define testable hypotheses, and shape our experimental research strategy.