The C. elegans Germline: A Test Tube for Cell and Developmental Biology

线虫种系：细胞和发育生物学的试管

• 批准号: 10794670
• 负责人: David Irwin Greenstein
• 金额: $ 1.01万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10794670
• 关键词: Administrative Supplement; Award; Bachelor' s Degree; Biological Models; Biomedical Research; CRISPR/Cas technology; Caenorhabditis elegans; Cellular biology; Congenital Abnormality; Data; Databases; Defect; Degree program; Development; Developmental Biology; Doctor of Philosophy; Effectiveness; Embryo; Embryonic Development; Ensure; Ethics; Faculty; Fertilization; Funding; Gametogenesis; Generations; Genes; Genome; Germ Cells; Human; Human Biology; Infertility; Laboratories; Maternal Messenger RNA; Meiosis; Mentors; Messenger RNA; Molecular; Molecular Analysis; Nematoda; Oocytes; Organelles; Parents; Positioning Attribute; Process; Proteins; RNA-Binding Proteins; Reproduction; Research; Scientist; Signal Transduction; Spontaneous abortion; System; Testing; Time; Training; Translational Regulation; Tube; United States National Institutes of Health; career; embryo stage 2; genome editing; graduate school; interest; next generation; programs; undergraduate student

Summary The earliest stages of embryonic development are guided by mRNAs, proteins, and organelles provided by the maternal germline. As the embryo switches from maternal to zygotic control, mechanisms are deployed to clear maternal mRNAs from the embryo after they have completed their functions. The molecular mechanisms of maternal mRNA clearance are incompletely understood but are of intensive interest for the field. We recently discovered that a highly conserved RNA-binding protein is required for maternal mRNA clearance in the nematode Caenorhabditis elegans. Remarkably, we found many mRNAs that are associated with this protein (SPN-4) in oocytes are rapidly destabilized and cleared after fertilization. We are testing the hypothesis that SPN-4 clears many of its associated mRNAs in somatic blastomeres through its association with the CCR4-NOT deadenylase, which functions in mRNA destabilization. Mentoring the next generation of scientists has been a central component and benefit of NIH’s longstanding support for this R35 award and its predecessor R01. During the course of this research program, the PI has mentored scientists at every level—from undergraduate students to faculty. The C. elegans molecular system provides an ideal format for training young scientists to conduct hypothesis-driven research. The generation time is 3.5 days at 20°C. The worms are transparent and germ cells, gametes, and embryos can be directly observed, as can the process of oocyte development, meiotic maturation, and fertilization. The complete genome sequence and a well-annotated database facilitates molecular analysis. Methods for CRISPR-Cas9 genome editing are robust and are routinely conducted by undergraduate students in our laboratory. The evolutionary conservation of many developmental control genes ensures the wide relevance of our findings to human biology. This effort has had substantial benefits for the effectiveness this funded research program, as well as for more broadly contributing to the scientific workforce. This administrative supplement to the parent award seeks to mentor an undergraduate student, who has been working in the PI’s laboratory and who is committed to a career in biomedical research. This training will position her well for applying to graduate school to pursue a PhD degree upon completion of her undergraduate degree program.

总结 胚胎发育的最早阶段是由基因组提供的mRNA、蛋白质和细胞器指导的。 母系生殖系当胚胎从母体控制切换到合子控制时， 母体mRNA在完成其功能后从胚胎中分离出来。的分子机制 母体mRNA清除还不完全清楚，但对该领域具有强烈的兴趣。我们最近 发现一种高度保守的RNA结合蛋白是母体mRNA清除所必需的。 线虫线虫值得注意的是，我们发现了许多与这种蛋白质相关的mRNA， 在受精后，卵母细胞中的SPN-4迅速不稳定并被清除。我们在验证一个假设 SPN-4通过与CCR4-NOT结合，清除体细胞卵裂球中许多与其相关的mRNA。 去腺苷酶，其在mRNA去稳定化中起作用。指导下一代科学家一直是一个 NIH长期支持这项R35奖及其前身R01的核心组成部分和好处。期间 在这项研究计划的过程中，PI指导了各个层次的科学家--从本科生到 教师。梭elegans分子系统提供了一个理想的形式，培养年轻的科学家进行 假设驱动的研究。在20 ° C下，世代时间为3.5天。蠕虫是透明的，生殖细胞， 配子和胚胎，以及卵母细胞发育，减数分裂成熟， 和受精。完整的基因组序列和注释良好的数据库有助于分子分析。 CRISPR-Cas9基因组编辑的方法是稳健的，并且由本科生常规进行 在我们的实验室里。许多发育控制基因的进化保守性确保了广泛的 我们的发现与人类生物学的相关性。这一努力对有效性产生了实质性的好处， 资助的研究计划，以及更广泛地为科学劳动力做出贡献。这一行政 家长奖的补充旨在指导一名本科生，他一直在PI工作， 实验室和世卫组织致力于生物医学研究的职业生涯。这次培训将使她在申请时处于有利地位 在完成本科学位课程后，她将进入研究生院攻读博士学位。