This application is for the first competing renewal of our pre-doctoral training program on The Molecular Pathogenesis of Infectious Diseases at the University of Colorado School of Medicine. This emerging area of research encompasses molecular biological and biochemical studies on microbial virulence factors, host resistance mechanisms, regulation of gene expression during infection, structure-function analysis of microbial and host cell molecules that play key roles in infections, analysis of interactions of bacteria and viruses with differentiated host cells in vitro, and studies on bacterial and viral infections in animal models using either wild type or genetically modified strains of microbes and host animals. The highly interactive members of our training faculty have proven productivity for innovative research in these areas, successful research funding from NIH and other granting agencies, and extensive experience in training pre-doctoral students in the multidisciplinary approaches needed for cutting edge research on the pathogenesis of infectious diseases. In addition to performing their mentored research projects, our trainees will participate in a comprehensive program of didactic courses, seminars, journal clubs, and research-in-progress meetings which will train them to identify important new research questions, design well-controlled experiments using a wide variety of molecular, cellular and in vivo techniques, critically evaluate and present their results, and understand and apply principles of ethics to their research. Students are selected for appointment to this training program only after they have completed all of their required courses, passed their preliminary and comprehensive examinations and begun their dissertation research. The breadth of our integrated, interdepartmental training program will prepare students for innovative careers in academia or biotechnology. This dynamic new training program has been extremely successful. It has fostered new research collaborations and grants, improved the curriculum, and fostered interdisciplinary interactions among the pre-doctoral trainees. In the 4 years since our training program on the Molecular Pathogenesis of Infectious Diseases began, our training faculty increased from 19 to 21, and the steady state number of predoctoral trainees in faculty labs grew from 21 to 31. Currently this training grant provides only one year of support for 3 trainees each year. We request 4 positions in years 06-07 to provide a 2-year commitment for 1 of the 3 trainees appointed each year and 5 positions in years 08-10 to fund one additional trainee whose research will focus on molecular mechanisms of infection related to biodefense or emerging infectious disease agents.