The goal of this study is to obtain experience, training, and expertise in disease pathogenesis while performing experiments designed to elucidate the role of C. pneumoniae in the development and progression of atherosclerosis. This study is an extension of previous work and involves the implementation of a broader scope of research and technical skills. These experiments will be conducted using mouse systems; specifically, the apoE-deficient transgenic mouse and the C57BL/6J mouse strains. Phase I, during Years 1-3, will be devoted to learning and applying the techniques of morphometric analysis to show whether C. pneumoniae infection augments atherosclerotic lesion development and cell type-specific immunocytochemical staining to determine if C. pneumoniae stimulates a heightened inflammatory response within the atherosclerotic plaque. Phase II, to be implemented during Years 4 and 5, will involve the application of cellular and molecular approaches to study the mechanistic basis of the role of C. pneumoniae in atherosclerosis. These studies will necessitate the acquisition of techniques in differential immunocytochemistry and in situ hybridization. Future experiments utilizing these approaches in therapeutic intervention studies will be the focus of future grant applications. This project will be carried out under the direction of well-established investigators in the fields of Chlamydia and atherosclerosis, and will enable the candidate to continue successfully and competitively in the field of chylamydial disease pathogenesis, in either the academic or private research sectors.
