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.

概括 胚胎发育的最早阶段是由mRNA，蛋白质和细胞器指导的 产妇种系。随着胚胎从母体切换到合子控制，部署了机制以清除 孕产妇在完成功能后的胚胎mRNA。分子机制 母体mRNA清除率不完全理解，但对该领域具有密集的兴趣。我们最近 发现在孕产妇mRNA清除中需要高度保守的RNA结合蛋白 线虫秀丽隐杆线虫。值得注意的是，我们发现许多与该蛋白质相关的mRNA （SPN-4）卵母细胞在受精后迅速稳定和清除。我们正在检验以下假设 SPN-4通过其与CCR4相关联在体细胞囊体中清除了许多相关的mRNA denenylise，在mRNA不稳定中起作用。指导下一代科学家一直是 NIH对R35奖及其前身R01的长期支持的中心部分和利益。期间 该研究计划的过程，PI从本科生那里指导了科学家 到教师。秀丽隐杆线虫分子系统为训练年轻科学家进行进行提供理想的格式 假设驱动的研究。在20°C时的生成时间为3.5天。蠕虫是透明的，生殖细胞， 可以直接观察到游戏和胚胎，卵母细胞的发展过程，减数分裂成熟，也可以直接观察到 和受精。完整的基因组序列和良好的数据库最爱分子分析。 CRISPR-CAS9基因组编辑的方法很强，并且是本科生常规进行的 在我们的实验室。许多发育控制基因的进化保护可确保广泛 我们的发现与人类生物学的相关性。这项努力为有效性带来了重大好处 资助的研究计划以及更广泛地为科学劳动力做出了贡献。这个行政 父母奖的补充旨在指导一名本科生，他一直在PI的工作 实验室以及致力于生物医学研究职业的人。这项培训将使她申请良好 研究生院完成博士学位后，她的本科学位课程完成了博士学位。