Dissecting the Regulation of Gene Expression during C. elegans Embryogenesis

描述（由申请人提供）：我建议开发工具、数据集和方法，用于对秀丽隐杆线虫胚胎发育过程中转录因子调控的基因进行全基因组鉴定。在职业发展阶段，我将使用我们在沃特斯顿实验室开发的方法来生成线虫胚胎中具有细胞分辨率的转录因子活性的初始图谱。与此同时，我将开发技术来促进胚胎中转录因子下游靶点的有效识别。一旦进入我自己的实验室，我将扩展这些方法，以在基因组规模上识别和表征许多转录因子的功能靶点，并探索转录因子如何结合起来调节基因表达。职业发展阶段对于这项工作至关重要，因为需要开发方法，而且我建议生成的转录因子表达图谱将提供一个关键的整合平台，供在选择全基因组分析因子和解释结果数据时使用。 与公共卫生的相关性：了解转录因子在发育过程中如何发挥作用，可以提供有关相同转录因子在不适当激活时如何在癌症中发挥作用的信息。此外，本研究中确定的受发育重要转录因子调节的人类基因直系同源物可能在正常发育和疾病中发挥作用。

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.