Klaus Hahn (Pharmacology), John Sondek (Pharmacology), Keith Burridge (Cell and Developmental Biology), Alan Hall (Sloan-Kettering Institute), and Gaudenz Danuser (UT Southwestern) have been awarded a 5-year Program Project Grant from the National Institutes of Health to study GEF/Rho GTPase signaling circuitry. Rho family GTPases are ubiquitous molecular switches that control extraordinarily diverse cellular processes. They are activated by guanine nucleotide exchange factors (GEFs) that are roughly 5-fold more numerous than the GTPases themselves and integrate the many cellular inputs controlling GTPase function. GEFs and GTPases form complex networks that are constituted transiently and locally for specific purposes. Biochemical, genetic, molecular, and structural analyses have unraveled a great deal about these critically important pathways, but their spatio-temporal regulation can only be fully understood in the context of intact cells. This PPG consists of 4 projects and brings together team members with diverse expertise to develop innovative technologies enabling the study of GEF/GTPase networks in vivo, computational tools to extract network architecture and signaling kinetics from imaging data, and in-depth knowledge of cell behaviors critically dependent on GEF/GTPase dynamics.