INTERNATIONAL RESEARCH SCIENTIST DEVELOPEMENT AWARD

候选人研究的长期目标是确定宿主遗传学对蠕虫共感染免疫反应的影响。拟议的研究通过检查美洲钩虫和曼氏血吸虫共流行地区居民的细胞免疫反应，使他朝着这一目标迈进。候选人将进行一项纵向研究，其中他(a)将共同流行地区的居民聚集到扩展的多家庭谱系中，(b)在抗蠕虫治疗前和一年后使用流式细胞术分析识别与蠕虫共感染相关的细胞免疫反应，以及(c)确定这些细胞免疫反应的变化有多少可以划分为遗传，系统环境和随机环境成分。拟议研究的平行教学目标包括(a)培训收集家谱数据和在扩展的多户家谱中取样的方法；(b)单色和双色流式细胞术分析的指导，包括细胞内染色以产生选定的T细胞来源的细胞因子；(c)在定量遗传分析方法方面的培训，以确定遗传学对细胞免疫反应变异的影响。拟议研究的国外部分将于01年和02年在巴西的Rene Rachou中心进行流式细胞术分析培训。03年，候选人在西南生物医学研究基金会接受数量遗传学培训。这一建议鼓励跨学科性质的候选人的长期职业目标，通过整合实验室工作与定量遗传学的统计方法。它还强调了这种研究的实践性，将上述学习目标组织到蠕虫共感染的纵向研究序列中。

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.