Comparative transcriptomics for nematode development

描述（由申请人提供）：我的主要研究目标是根据进化理论方法破译发育中的转录控制。发育生物学中一个长期存在的问题是确定多细胞生物体发育过程中非常强大的事件网络的遗传基础。线虫C.在这方面，秀丽隐杆线虫是一个方便的模型，它展示了细胞自主和细胞间通讯的发育模式。虽然这种生物体的高度一致的细胞谱系已经得到了很好的研究，揭示了一些主要的调节因子，但对于在整个发育过程中作用于参与基因的约束却知之甚少。我们假设野生C. elegans分离株和现存的小杆线虫物种之间的关系将揭示分子细节上的进化可塑性过程。我们的方法涉及比较，在基因的基因基础上，两个进化的时间框架的效果：通过比较野生菌株和宏观进化通过比较不同的小杆线虫物种的微观进化。如果在线虫中检测到足够的变异，则比较转录组学数据有望通过识别每个基因的每个时间点的进化模式（纯化、阳性和中性）来解决可用的时间过程数据。这些预测模式的实验测试通过使用反向遗传学和转基因菌株的一组基因与有趣的保守性和基因表达的分歧。

DESCRIPTION (provided by applicant): My primary research objective is to decipher transcriptional control in development based upon an evolutionary theoretic approach. A long-standing problem in developmental biology is to determine the genetic basis for the remarkably robust network of events that specify the development of a multicellular organism. The nematode C. elegans makes for a convenient model in this effort, exhibiting both cell-autonomous and cell-cell communication modes of development. While the highly uniform cell lineage of this organism has been elegantly studied, revealing a number of master regulators, little is known about the constraints that act upon the participating genes throughout development. We hypothesize that a comparison among wild C. elegans isolates and with extant Caenorhabditis species would reveal the evolutionary plasticity of the process in molecular detail. Our approach involves comparing, on a gene by gene basis, the effect of two evolutionary time frames: micro-evolution through a comparison of wild isolates and macro-evolution through a comparison with divergent Caenorhabditis species. Provided that sufficient variation is detected among the nematodes, the comparative transcriptomic data promises to resolve the available time course data by identifying the mode of evolution (purifying, positive, and neutral) for each time point of each gene. These predicted modes are experimentally tested by the use of reverse genetics and transgenic strains for a set of genes with interesting conservation and divergences in gene expression.