We propose an interdisciplinary research project at the frontline of molecular structural biology to dissect the interaction of a novel cytokine, interleukin 34, with its hematopoietic RTKIII receptor, Colony Stimulating Factor1 Receptor. The proposed research project aims to elucidate the structural, kinetic and thermodynamic determinants that dictate this unusual cytokinereceptor specificity, using both experimental and computational methods in structural biology.