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 Factor-1 Receptor. The proposed research project aims to elucidate the structural, kinetic and thermodynamic determinants that dictate this unusual cytokine-receptor specificity, using both experimental and computational methods in structural biology.