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.

在生活系统中，基因表达中的噪声也会导致表型的差异，即使在遗传相同的细胞中也可能导致。该项目将使用线虫C.秀丽隐杆线虫中的肠发展作为模型，研究携带相同基因型的动物中发生的不同表型的基础。控制肠道规范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被引入缺乏正常拷贝的秀丽隐杆线虫动物中。初步结果表明，只有一些胚胎使肠道产生肠道，而幸存的成年人的肠道异常。该项目将研究这些影响的基础。首先，将在高分辨率下检查最终突变胚胎中肠道的发育。其次，将与正常动物进行比较，在成年肠道中的全球基因表达，并将测试肠道规范途径中基因功能的可能缺陷。第三，将测量肠道规范上游最成分中噪声的来源，并且将鉴定出产物产物的基因的基因。将使用反向遗传学（使用RNA干扰），延时显微镜和表达基因（RNA-SEQ）的高通量测序。该实验将描述一组新的突变体中高分辨率的肠道发育，表征来自突变体菌株的成年肠道缺陷，并确定器官规范中基因表达噪声的可能来源。这项工作有可能定义生命系统如何管理开发过程中基因表达的内在差异的新范式。在执行这项工作的过程中，西班牙裔血统的PI将训练来自不同UC Riverside校园的大学生和研究生。一年级生物学大学生的实验室课程将培训学生的研究，并允许他们进行原始研究。