PROJECT SUMMARY The goal of the Protein-Metabolite Interactomics Core (PMIC) is to advance the understanding of protein- protein and protein-metabolite interactions in relation to iron, heme, hematopoiesis and red cell biology. We have developed a highly innovative approach to identify protein-metabolite interactions that regulate protein function. This approach is termed Mass spectrometry Integrated with equilibrium dialysis for the Discovery of Allostery Systematically or MIDAS, which utilizes purified proteins and a metabolite library to discover interactions between any soluble protein of interest and components of a defined metabolite library. We have validated our approach and shown that this platform, based on equilibrium dialysis, detects known and novel metabolite-protein interactions with very high sensitivity, independent of specific assays of protein function. This novel approach is able to discover unappreciated interactions that result in regulation of protein function. The CIHD will utilize the expertise provided by the existing U0fU Proteomics Core to provide a unique approach to discovery in the area of iron and heme homeostasis focused on combating nonmalignant hematologic diseases.