Dissecting the Regulation of Gene Expression during C. elegans Embryogenesis

项目描述（申请人提供）：本人拟开发工具、数据集和方法，用于全基因组鉴定秀丽隐杆线虫胚胎发育过程中受转录因子调控的基因。在职业发展阶段，我将使用我们在Waterston实验室开发的方法，在秀丽隐杆线虫胚胎中生成具有细胞分辨率的转录因子活性的初始图谱。同时，我将开发技术，以促进胚胎中转录因子下游目标的有效鉴定。一旦进入我自己的实验室，我将扩展这些方法，在基因组尺度上识别和表征许多转录因子的功能靶标，并探索转录因子如何结合来调节基因表达。职业发展阶段对这项工作至关重要，因为需要开发方法，因为我提出的转录因子表达图谱将提供一个关键的集成平台，用于选择全基因组分析的因子和解释结果数据。

DESCRIPTION (provided by applicant): I propose to develop tools, datasets and methods for the genome-wide identification of genes regulated by transcription factors during the embryonic development of Caenorhabditis elegans. During the career development phase, I will use methods we have developed in the Waterston lab to generate an initial map of transcription factor activity with cellular resolution in the C. elegans embryo. In parallel I will develop technology to facilitate the efficient identification of downstream targets of transcription factors in the embryo. Once in my own lab, I will extend these methods to identify and characterize functional targets of many transcription factors on a genomic scale and to explore how transcription factors combine to regulate gene expression. The career development phase will be critical for this effort because of the need for development of methods, and because the transcription factor expression map I propose to produce will provide a critical integrating platform to use when choosing factors for genome-wide analysis and when interpreting the resulting data. Relevance to public health: Knowledge of how transcription factors act in development may provide information about how the same transcription factors function in cancers when inappropriately activated. Furthermore, human orthologs of genes identified in this study as regulated by developmentally important transcription factors may play roles in both normal development and disease.