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 胚胎开发的最早阶段是mRNA的指导 母体种系，作为胚胎从母体切换到合子控制 一年后胚胎的母体mRNA构成了它们的功能。 母体mRNA清除率不完全理解，但对于我们最近的领域来说是密集的 发现在孕妇母体mRNA清除率中需要高度保守的RNA结合蛋白 线虫秀丽隐杆线虫。 （SPN-4）卵母细胞在受精后迅速稳定和清除。 SPN-4通过与CCR4相关的smatic胚泡中清除了许多相关的mRNA denenylise，在mRNA不稳定中起作用。 NIH对R35奖的长期支持，是R01 在此Cearch计划的过程中，PI在每个级别都指导了科学家 - 从地下学生开始 教师。 假设驱动的研究时间为20°C 3.5天。蠕虫是透明的，生殖细胞， 可以直接观察配子和胚胎，卵母细胞发育，减数分裂成熟的过程也可以观察到 和施肥。 CRISPR-CAS9基因组编辑的方法是强大的，并且是常规的地下学生进行的。 在我们的实验室中。 我们的发现与人类生物学的相关性。 资助的研究计划以及更大的科学劳动力 父母奖的供应旨在指导一名本科生，他一直在PI的工作 实验室和致力于 在组成她的地下学位课程后，要攻读博士学位。