Project Summary We propose to acquire a NanoTemper Monolith NT-Auto, with detection of both fluorescently-labeled molecules and of intrinsic fluorescence. This instrument provides maximum flexibility for investigators and will be the only instrument of its kind in the Boston area. The Monolith instruments measure microscale thermophoresis, which is based on the generation of a precise temperature gradient while monitoring changes in sample migration along this gradient, as detected by sample fluorescence to determine binding. The changes in migration of molecules along the temperature gradient reflect changes in molecular hydration shell, charge, or size; as one or all of these parameters change upon ligand binding, differences in the bound and unbound states can be determined. The requested instrument allows determination of binding affinities, oligomerization, and other parameters without immobilization. The instrument will be used to advance numerous projects related to cancer, antibiotic resistance, infectious disease, viral replication, inflammation, and neurological disorders including addiction. A second major focus is on drug design, development, and delivery.