Comparative transcriptomics for nematode development

线虫发育的比较转录组学

• 批准号: 7198081
• 负责人: ITAI YANAI
• 金额: $ 5.2万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-06 至 2009-03-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7198081
• 关键词: Address; Biological Assay; Caenorhabditis; Caenorhabditis elegans; Cell Communication; Cell Lineage; Cells; Custom; Data; Data Set; Development; Developmental Biology; Embryo; Embryonic Development; Event; Evolution; Exhibits; Facility Construction Funding Category; Family; Fellowship; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Polymorphism; Hawaiian population; Human; Individual; Maintenance; Modeling; Molecular; Molecular Profiling; Morphogenesis; Names; Nematoda; Numbers; Oligonucleotide Microarrays; Organism; Pattern; Phase; Population; Process; Purpose; Regulation; Research; Sampling; Specific qualifier value; Staging; Techniques; Testing; Time; Transcript; Transcriptional Regulation; Transgenic Organisms; Variant; base; comparative; density; gene function; interest; positional cloning; research study; transcriptomics

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.

描述（由申请人提供）：我的主要研究目标是基于进化理论方法在开发中解密转录控制。发育生物学的一个长期存在的问题是确定指定多细胞生物发展的事件网络的遗传基础。线虫秀丽隐杆线虫在这一努力中建立了方便的模型，表现出细胞自主和细胞电池的发育模式。尽管该生物的高度均匀的细胞谱系进行了优雅的研究，揭示了许多主要调节剂，但对整个发育过程中参与基因的约束知之甚少。我们假设野生曲霉分离株和与现存的Caenorhabditis物种之间的比较将揭示该过程的进化可塑性，以分子细节。我们的方法涉及根据基因的基因比较两个进化时帧的效果：通过比较野生分离株和宏观进化，通过与发散的caenorhabditis物种进行比较。只要在线虫之间检测到足够的变化，比较转录组数据有望通过识别每个基因的每个时间点的进化方式（净化，正和中性）来解决可用的时间过程数据。这些预测的模式通过使用反向遗传学和转基因菌株对一组具有有趣的保守性和基因表达差异的基因进行实验测试。