Project Summary This pre-doctoral Pharmacological Sciences Training Program (PSTP) is a cross-disciplinary program that represents a merger of research training opportunities in the Schools of Medicine (Pharmacology) and Pharmacy (Medicinal Chemistry and Pharmaceutics) at the University of Washington. The rationale for this program is that it is essential for providing in-depth training in several inter-related disciplines that are central to current and future research related to the discovery, validation and development of new drug targets and new chemical entities that will improve global health. This focus distinguishes training provided by the PSTP from other pre-doctoral training grants available at UW. The primary objective of the PSTP is to develop scientists, equipped with the necessary background in the biological and chemical sciences and training in the application of modern tools of research and instrumental techniques, to undertake and direct fundamental research related to drug action, metabolism and pharmacokinetics. Trainees follow tracks that emphasize training in four broadly defined areas: (I) cellular and molecular pharmacology, (II) structure and drug/vaccine design, (III) drug metabolism, (IV) pharmacokinetics, drug transport and delivery, which exist in the departments of Pharmacology, Medicinal Chemistry and Pharmaceutics. Didactic components involve individualized, highly multidisciplinary programs of coursework and seminars that are centered on the biological and chemical sciences. Additional program elements include a PSTP-specific journal club, a 'career' day that brings scientists from varied 'nontraditional careers' to speak with trainees, industry mentors and internships, and recently added emphasis on rigor and reproducibility. The program brings together 34 well-funded faculty members whose research emphasizes training in mechanisms and regulation of cell signaling, neuropharmacology, structural analysis of pharmacologically relevant protein-ligand interactions, mechanistic and bio- analytical aspects of drug metabolism and toxicology, pharmacogenetics, pharmacokinetics/dynamics and drug transporter function and regulation. Under-represented and disadvantaged students, who are actively recruited through a number of faculty activities, currently represent ~33% of the training cohort. In this competitive renewal of the Pharmacological Sciences National Research Service Award program, support is requested for 13 pre-doctoral trainees per year. The selection of trainees will be on a competitive basis from the pool of students in years 1-3, who are committed to research in one of the aforementioned areas.