INTERNATIONAL RESEARCH SCINTIST DEVELOPEMENT AWARD

候选人研究的长期目标是确定宿主遗传学对蠕虫合并感染免疫反应的影响。 拟议中的研究通过检查美洲钩虫和曼氏血吸虫共同流行地区居民的细胞免疫反应来推动他实现这一目标。 候选人将进行一项纵向研究，其中他（a）将共同流行区的居民聚集到扩展的多户谱系中，（B）在抗蠕虫治疗之前和之后一年使用流式细胞术分析鉴定与蠕虫共同感染相关的细胞免疫应答，以及（c）确定这些细胞免疫应答中的变异有多少可以分为遗传、系统环境、和随机的环境成分。 拟议研究的并行教学目标包括：（a）家谱数据收集和扩展多户谱系采样方法的培训;（B）单色和双色流式细胞仪分析教学，包括细胞内染色以产生选定的T细胞衍生细胞因子;和（c）定量遗传分析方法的培训，以确定遗传学对细胞免疫应答变化的影响。 拟议研究的外国部分将于01年和02年在Centro de Pesquisas Rene Rachou（巴西）进行流式细胞术分析培训。 在03年，候选人在西南生物医学研究基金会接受定量遗传学培训。 这项建议鼓励候选人的长期职业目标的跨学科性质，通过整合实验室的实验室工作与数量遗传学的统计方法。 它还强调了这种研究的实用性，通过将上述学习目标结构化为蠕虫合并感染纵向研究的序列。

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.