This is a competing renewal for the North Carolina Program Project on Sexually Transmitted Diseases. This group has been in existence for 10 years, and throughout this time has emphasized use of the tools of molecular biology, biochemistry, and cell Physiology of understand important problems in the pathogenesis, host response and epidemiology of several different sexually transmitted diseases. Particular emphasis has been placed on gonococcal infections. For the upcoming 5 years, 5 integrated projects are presented plus an administrative core support projects. Project 1 (P. F. Sparling, PI), will examine the biochemical mechanisms of gonococcal iron uptake from sources available in humans. The structure and function of several common surface exposed proteins thought to be involved in iron uptake will be investigated by use of recombinant DNA techniques. Project 2 (J. Cannon, PI) will examine the molecular mechanisms for phase and antigenic variation of one of the gonococcal outer membrane proteins, Protein II, as well as the structure and function of a novel gonococcal outer membrane lipoprotein designated H.8. Project 3 (M. Cohen, PI) will investigate the interactions between gonococci and polymorphonuclear neutrophils and related cells, with emphasis on the genetics and biochemistry of gonococcal responses to oxidant and other stresses. Project 4 (P. Wyrick, PI) will investigate the pathogenesis of genital chlamydia using a novel human endometrial cell tissue culture assay perfected by her laboratory. The same endometrial cell model also will be used by collaborating investigators in Projects 1, 2 and 3 to investigate mechanisms of gonococcal Pathogenicity. Project 5 (P. Bassford, PI) will examine the metabolism of Treponema pallidum, using molecular genetic techniques to isolate a wide variety of T. Pallidum genes in E. coli hosts. Because of the extensive interactions between component projects we are confident that the group is much more powerful than the sum of the individual component parts. The activities of the PPG include members of the faculty from the Depts. of Medicine, Microbiology & Immunology, and Biochemistry in the School of Medicine and also from the Dept. of Parasitology & Laboratory Practice in the School of Public Health. These activities are also coordinated with related units (SID clinics, AIDS Clinical Study Group) of the University of North Carolina at Chapel Hill and with the Durham County Health Department in Durham, N.C.
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