Developmental Buffering in a Gene Regulatory Network

基因调控网络中的发育缓冲

• 批准号: 1258054
• 负责人: Morris Maduro
• 金额: $ 55万
• 依托单位: University of California-Riverside
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-15 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1258054&HistoricalAwards=false
• 关键词: Developmental; Buffering; Gene; Regulatory; Network

In living systems, noise in gene expression can lead to differences in phenotype, even among genetically identical cells. This project will study the basis for different phenotypes occurring in animals carrying the same genotype, using the development of the gut in the nematode C. elegans as a model. The genetic pathway controlling specification of the gut involves transient activation of the genes end-1 and end-3. Mutated versions of these genes have been introduced into C. elegans animals that lack the normal copies. Preliminary results show that only some embryos make gut, and that surviving adults have abnormal guts. This project will study the basis for these effects. First, the development of the gut in end mutant embryos will be examined at high resolution. Second, global gene expression in adult guts will be compared with normal animals, and possible defects in function of genes in the gut specification pathway will be tested. Third, sources of noise in the upstream-most components of gut specification will be measured, and genes whose products influence the stochastic specification of gut will be identified. Reverse genetics (using RNA interference), time lapse microscopy, and high-throughput sequencing of expressed genes (RNA-Seq) will be used. The experiments will describe gut development at high resolution in a new set of mutants, characterize defects in adult intestines derived from the mutant strains, and identify possible sources of gene expression noise in organ specification. The work has the potential to define new paradigms for how living systems manage inherent differences in gene expression during development. In the course of performing this work, the PI, himself of Hispanic descent, will train undergraduates from the diverse UC Riverside campus, and a graduate student. A laboratory course for first-year Biology undergraduates will train students in research and allow them to carry out original research.

在生命系统中，基因表达中的噪音会导致表型的差异，即使是在基因相同的细胞中。本项目将利用线虫C的肠道发育，研究携带相同基因型的动物发生不同表型的基础。优雅的模特控制肠道特化的遗传途径涉及基因end-1和end-3的瞬时激活。这些基因的突变版本已经被引入C。缺少正常拷贝的线虫动物。初步结果显示，只有一些胚胎能制造肠道，而存活下来的成年人则有异常的肠道。本项目将研究这些影响的基础。首先，将以高分辨率检查末端突变胚胎中肠道的发育。其次，将成年肠道中的整体基因表达与正常动物进行比较，并将测试肠道特化途径中基因功能的可能缺陷。第三，噪声的来源，在最上游的肠道规格的组件将被测量，其产品的影响肠道的随机规格的基因将被识别。将使用反向遗传学（使用RNA干扰）、延时显微镜和表达基因的高通量测序（RNA-Seq）。这些实验将在一组新的突变体中以高分辨率描述肠道发育，表征来自突变菌株的成人肠道缺陷，并确定器官规格中基因表达噪音的可能来源。这项工作有可能为生命系统如何在发育过程中管理基因表达的固有差异定义新的范式。在执行这项工作的过程中，PI，自己的西班牙裔，将培训本科生从多样化的加州大学滨江校园，和一名研究生。生物学本科一年级的实验室课程将培养学生的研究能力，并允许他们进行原创性研究。