Support is requested for 9 predoctoral and 6 postdoctoral positions to establish a training program in the interdisciplinary area of Pharmacoinformatics. This program is proposed because current approaches to the discovery of new drugs have not fully capitalized on advances in bioinformatics, genomics, computing and other fields, and consequently, the rate of drug discovery has lagged behind breakthroughs in these areas. The pipeline of new drugs under development has not increased in recent years, and a very small number of new drags are thus responsible for bearing the enormous costs of an increasingly expensive process that evolved prior to development of massive amounts of new information and the ability to integrate it into usable and accessible systems. We propose a comprehensive, integrated program to train the next generation of scientists to: (1) use informatics approaches to identify biomolecules that are candidates for drug targeting, (2) use structural genomics, chemoinformatics, and structure-based design to develop families of chemicals to target selected biomolecules and structures, and (3) use ADMET (absorption, distribution, metabolism, elimination, and toxicity) profiling and computational predictions of efficacy to select viable drag candidates prior to biological testing. Training will emphasize in silico approaches to achieve these goals. Inter-institutional training will be conducted by sixty-three training faculty from the six institutions of the Gulf Coast Consortia (Baylor College of Medicine, M. D. Anderson Cancer Center, Rice University, the University of Houston, The University of Texas Health Science Center at Houston, and The University of Texas Medical Branch at Galveston) in the Houston -Galveston area and will utilize research training with co-mentors, didactic courses, seminars, retreats, and career development activities. Predoctoral trainees will matriculate and receive first year support at their home institutions, and stipends will be awarded on a competitive basis for years 2-4 of graduate training. The home institution will award the Ph.D. Postdoctoral trainees will receive support for two years maximum. The proposed program is designed to train future leaders in drag discovery research.
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