Project Summary Chemical Biology tools for probing, manipulating, and imaging biological systems can provide deep insights into fundamental processes. Chemical dimerization and protein localization strategies, fluorescent probes and sensors for analyte detection, and small molecules for perturbing biological pathways and process have become important research tools for gleaning deeper insight into biological processes. The development of optically triggered variants of these important chemical biology tools has provided new and more powerful approaches to probing, manipulating, and imaging key pathways and processes with new levels of spatial and temporal control not previously available. Despite the utility of molecular chemical biology approaches, many of the tools and reagents are not readily available due to the need for on-demand synthesis and molecular customization depending on the pathways and processes being studied and the lack of commercially availability. The proposed Chemical Biology and Materials Core will solve these problems by working directly with the individual projects of the program to design, synthesize, and implement cutting edge Chemical biology tools customized to the project research aims. The Chemical Biology Core will also serve as a resource throughout the award period to develop new approaches and implement key technologies in synergy with the MAC core and individual projects. In Aim 1 the core will develop chemical dimerizers for optogenetic control of key biomolecule localization and activation events. In Aim 2 the core will develop peptide based chemical probes for interrogation of key biological pathways and processes.