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合并感染的免疫反应的影响。这项拟议的研究通过检测美洲坏疽和曼氏血吸虫共同流行地区居民的细胞免疫反应，推动了他实现这一目标。候选人将进行一项纵向研究，其中他(A)将共流行地区的居民聚集到扩展的多家庭家系中，(B)在抗蠕虫治疗之前和一年后使用流式细胞仪分析与蠕虫合并感染相关的细胞免疫反应，以及(C)确定这些细胞免疫反应中的多少变异可以划分为遗传、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)培训多家庭扩展家系的家谱数据收集和抽样方法；(B)教授单色和双色流式细胞术分析，包括细胞内染色以产生选定的T细胞衍生细胞因子；(C)培训定量遗传分析方法，以确定遗传对细胞免疫反应变化的影响。拟议研究的外国部分将于01年和02年在雷内·拉丘中心(巴西)进行流式细胞仪分析培训。03年，考生在西南生物医学研究基金会接受数量遗传学培训。这项建议通过将实验室基准工作与数量遗传学的统计方法相结合，鼓励候选人长期职业目标的跨学科性质。它还强调了这种研究的实际性质，将上述学习目标组织成关于蠕虫合并感染的纵向研究序列。

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.