RUI: Functional analysis of the exon junction complex in planarian stem cells and regeneration

RUI：涡虫干细胞外显子连接复合物的功能分析和再生

• 批准号: 1656793
• 负责人: Jason Pellettieri
• 金额: $ 47.44万
• 依托单位: Keene State College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1656793&HistoricalAwards=false
• 关键词: RUI; Functional; analysis; exon; junction

Non-Technical Paragraph: Many organisms, including humans, have some capacity to regenerate lost or damaged body parts following physical injury or disease. However, the extent of this ability varies considerably from one species to the next, and the biological mechanisms accounting for this variability are not well understood. This project will study genes that play a key role in the remarkable regenerative abilities of aquatic flatworms called planarians, animals that can re-form entire individuals from tiny body fragments in just over a week. Completion of the proposed objectives will advance our knowledge of how the large stem cell population that drives this process is regulated. Most research activities will be carried out by undergraduate students at Keene State College, providing valuable preparation for post-collegiate professional training and careers in the life sciences. Together with science outreach activities involving high school students, this will enhance New Hampshire's efforts to develop a technically proficient workforce crucial to further growth of the state's biotechnology and high-tech manufacturing industries.Technical Paragraph: This project will characterize post-transcriptional regulatory mechanisms governing gene expression in adult stem cells, using the planarian flatworm Schmidtea mediterranea as a model organism. Specifically, students will complete a functional analysis of the exon junction complex (EJC), a key regulator of RNA biochemistry with potentially conserved, yet poorly understood roles in stem cell biology. Prior work has established functions for the EJC in splicing, export of spliced mRNAs from the nucleus, translational control, and nonsense-mediated mRNA decay. The EJC has been linked to some gene-specific regulatory mechanisms during development; however, its biochemical function(s) and presumed RNA target(s) in self-renewing cell types in adult organisms are largely unknown. The research objectives of the current study will build upon preliminary data showing that the EJC is required for stem cell maintenance in planarians by: 1) Using RNAi and in situ hybridization to characterize the function and expression of EJC subunits during tissue homeostasis and regeneration; and 2) Combining candidate-gene and unbiased RNA-Seq approaches to identify EJC target RNAs. Completion of this research will enhance our understanding of molecular mechanisms governing gene expression in adult stem cells during tissue renewal and repair. The PI will undertake this work entirely with undergraduate and high school students to enhance STEM educational efforts in New Hampshire.

非技术段落：包括人类在内的许多生物具有某种能力，可以在身体损伤或疾病后再生损失或受损的身体部位。 但是，这种能力的程度因一个物种而异，而涉及这种变异性的生物学机制尚不清楚。 该项目将研究在一个称为平面虫的水生扁虫的显着再生能力中发挥关键作用的基因，它们可以在仅一周多的时间内从微小的身体碎片中重新形成整个个体。 拟议目标的完成将提高我们对如何调节这一过程的大型干细胞种群的了解。 大多数研究活动都将由基恩州立学院的本科生进行，为后大学后专业培训和生命科学职业提供宝贵的准备。 与涉及高中学生的科学宣传活动一起，这将增强新罕布什尔州开发技术熟练的劳动力，对该州的生物技术和高科技制造业的进一步增长至关重要。技术段落：该项目将在经过培养基层中使用类似于Planea的synera flatean schmids schmidtemt schmiden schmide schmid schmid schmide，该项目将表征后期转录的调节性调节性调节性的调节性调节性。 具体而言，学生将完成对外显子连接复合物（EJC）的功能分析，这是RNA生物化学的关键调节剂，具有潜在保守但知之甚少的干细胞生物学作用。 先前的工作已经建立了EJC在剪接，核中的剪接mRNA，翻译对照和胡说八道介导的mRNA衰变方面的功能。 EJC与开发过程中的某些基因特异性调节机制有关。然而，在成人生物体中，其生化功能（S）和假定的RNA靶标在很大程度上是未知的。 当前研究的研究目标将基于初步数据，表明EJC是在平面医生中维持干细胞所必需的：1）使用RNAi和原位杂交来表征组织稳态和再生期间EJC亚基的功能和表达； 2）结合候选基因和无偏的RNA-seq方法，以识别EJC靶标RNA。 这项研究的完成将增强我们对组织更新和修复期间成人干细胞中控制基因表达的分子机制的理解。 PI将完全在本科生和高中生中从事这项工作，以增强新罕布什尔州的STEM教育工作。