Project: Research project

Project Details


The purpose of this Program Project is to bring together collective
expertise in the areas of molecular biology, biochemistry and immunology,
and in vitro and in vivo models of mycobacterial disease, in order to
accumulate fundamental knowledge leading to a better understanding of the
nature of Mycobacterium avium, including the identification of drug
targets, whereby colonization and subsequent disseminated disease in AIDS
patients can be successfully treated. Project 1 will pursue the
biochemistry of M. avium in order to provide a detailed chemical knowledge
of the cell wall barrier, including those components unique to the group of
mycobacterial which may comprise specific drug targets. In addition, it
will investigate the basis of colony morphotypes, including the growing
body of evidence that relates the expression of the glycopeptidolipids to
persistence and virulence of the infection and resistance to chemotherapy.
Project 2 will address similar problems at the genomic level, specifically,
the cloning and analysis of genes for potential drug targets including
genes that encode essential enzyme systems and control the synthesis of
structures that determine morphotype, and hence potentially contribute to
the virulence of the organism and pathogenesis of disease. Project 3 will
continue to develop innovative animal models of M. avium infection, models
that most closely mimic the clinical situation in immunodeficient AIDS
patients. It will document the pathological process of colonization,
leading to active infection and disseminated disease in T cell-deficient
mice, and will relate this information to the molecular, biochemical, and
morphological properties of the isolate or variant. In addition, it will
provide a resource for the in vivo testing of potentially efficacious
compounds identified in Project 4. This last Project will directly address
the question of identifying drugs with activity against specific targets,
by combining computer modeling techniques with a sophisticated panel of in
vitro activity assays, prior to the testing of such agents in animal models
of infection.
Effective start/end date8/1/907/31/95


  • Medicine(all)
  • Immunology and Microbiology(all)