Project Summary The goal of this Diversity Supplement Application is to provide an in-depth research experience and strengthen the scientific background of Paola Marquez-Gomez to enable her to access and thrive at a graduate program or medical school. Toward this goal, Paola will work on an extension project of the paneer award engineering an orthogonal Gαs-coupled Designer G protein-couple receptor activated by designer drug (DREADD) to enable the multiplex activation of GPCR signaling pathways in mammalian cells. This work is significant because multiplex activation of GPCR signaling in mammalian cells would allow the study of GPCR signaling crosstalk and its effect on cellular phenotype, and, in the future, animal behavior. This work is innovative because it leverages experimental and chemoinformatics data to train a machine learning algorithm to engineer the substrate specificity of GPCRs for which no crystal structure is available.