The long-term objective of the candidate's research is to determine the influence of host genetics on the immune response to helminthic coinfection. The proposed research advances him toward this goal by examining the cellular immune response of residents in an area coendemic for Necator americanus and Schistosoma mansoni. The candidate will conduct a longitudinal study in which he (a) assembles the residents of the coendemic area into extended multi-household pedigrees, (b) identifies cellular immune responses associated with helminthic coinfection using flow cytometric analysis before and one year after anti- helminthic treatment, and (c) determines how much of the variation in these cellular immune responses can be partitioned into genetic, systematic environmental, and random environmental components. The parallel pedagogical goals of the proposed research include (a) training in the collection of genealogical data and methods for sampling in extended multi-household pedigrees; (b) instruction in single and double color flow cytometric analysis, including intracellular staining for the production of selected T cell derived cytokines; and (c) training in the methods of quantitative genetic analysis to determine the influence of genetics on the variation of the cellular immune responses. The foreign component of the proposed research takes place in years 01 and 02 at the Centro de Pesquisas Rene Rachou (Brazil) for training in flow cytometric analysis. In year 03, the candidate is at the Southwest Foundation for Biomedical Research for training in quantitative genetics. This proposal encourages the interdisciplinary nature of the candidate's long- term career goals by integrating laboratory benchwork with the statistical methods of quantitative genetics. It also emphasizes the practical nature of such research by structuring the above learning objectives into the sequence of a longitudinal study on helminthic coinfection.
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