CAREER: MicroRNA pathways controlling development after diapause in C. elegans

职业生涯：MicroRNA 途径控制线虫滞育后的发育

• 批准号: 1652283
• 负责人: Xantha Karp
• 金额: $ 74.6万
• 依托单位: Central Michigan University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-15 至 2023-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1652283&HistoricalAwards=false
• 关键词: CAREER; MicroRNA; pathways; controlling; development

NONTECHNICAL DESCRIPTION:In nature, animals grow up in different and often changing environments. Harsh environments such as cold weather or inadequate food can cause animals to slow their growth or even pause growth altogether. Despite this severe interruption to their development, if the environment improves, animals will continue their growth and ultimately become normal adults. The genes and proteins that allow animals to develop normally after a long interruption are unknown and are a major knowledge gap. This project builds on previous work from the PI to study this question in the microscopic nematode C. elegans. These worms are a valuable model because of their simplicity and ease of use for experiments. Furthermore, C. elegans shares 7,663 genes with humans, meaning that what we learn from C. elegans is often relevant across species. As part of this study, a new program will engage student teachers in research. This program will foster teacher-leaders who will then provide effective STEM education at the K-12 level. This education is critical for the US to maintain its leadership in scientific disciplines, and to provide students with skills that employers value. Furthermore, this study will result in the training of many undergraduate and graduate students, both in the PI's research lab and in lab-based courses taught by the PI.TECHNICAL DESCRIPTION:The proposed work capitalizes on the power of C. elegans as a model to elucidate mechanisms that enable development to occur normally after diapause. In favorable environments, C. elegans develops continuously through four larval stages separated by molts. In contrast, adverse environments promote entry into diapause ("dauer") midway through larval development. Despite this interruption, if favorable conditions are again encountered, development proceeds normally due to the modulation of developmental pathways and re-setting of cell fate. Prior work from the PI indicates that the potentiation of microRNA activity is a key component of the post-dauer developmental program. This project builds on that work to discover and characterize factors involved in post-dauer microRNA pathways. Preliminary data suggest that two transcription factors, ZTF-16 and FOXO/DAF-16, are important players in the post-dauer pathway. Genetic and molecular experiments will test the hypotheses that ZTF-16 is a microRNA target and that FOXO/DAF-16 is a modulator of microRNA activity. In addition, genomic approaches will identify factors that enable proper post-dauer development. Completing this project will define mechanisms by which microRNA pathways that control cell fate are modulated after dauer and lay the foundation for future work.

非技术描述：在自然界中，动物在不同且经常变化的环境中成长。 寒冷的天气或食物不足等恶劣环境会导致动物生长缓慢，甚至完全停止生长。 尽管它们的发育受到严重干扰，但如果环境改善，动物将继续生长并最终成为正常的成年人。 使动物在长时间中断后能够正常发育的基因和蛋白质尚不清楚，这是一个重大的知识差距。 该项目建立在 PI 之前的工作基础上，在微观线虫秀丽隐杆线虫中研究这个问题。 这些蠕虫是一种有价值的模型，因为它们简单且易于实验使用。 此外，秀丽隐杆线虫与人类共享 7,663 个基因，这意味着我们从秀丽隐杆线虫中学到的知识通常与跨物种相关。 作为这项研究的一部分，一项新计划将让实习教师参与研究。 该计划将培养教师领导者，他们将在 K-12 级别提供有效的 STEM 教育。 这种教育对于美国保持其在科学学科的领导地位并为学生提供雇主重视的技能至关重要。 此外，这项研究还将在 PI 的研究实验室和 PI 教授的实验室课程中对许多本科生和研究生进行培训。 技术描述：拟议的工作利用秀丽隐杆线虫作为模型的力量来阐明滞育后发育正常发生的机制。 在有利的环境中，线虫通过蜕皮分开的四个幼虫阶段连续发育。 相反，不利的环境会促进幼虫发育中途进入滞育（“dauer”）。 尽管存在这种中断，如果再次遇到有利的条件，由于发育途径的调节和细胞命运的重新设定，发育会正常进行。 PI 之前的工作表明 microRNA 活性的增强是后 dauer 发育计划的关键组成部分。 该项目以该工作为基础，旨在发现和表征参与后 dauer microRNA 途径的因素。 初步数据表明，两种转录因子 ZTF-16 和 FOXO/DAF-16 在后 dauer 通路中发挥着重要作用。遗传和分子实验将检验 ZTF-16 是 microRNA 靶标以及 FOXO/DAF-16 是 microRNA 活性调节剂的假设。 此外，基因组方法将确定能够实现适当的后发育的因素。 完成该项目将定义在 dauer 后调节控制细胞命运的 microRNA 途径的机制，并为未来的工作奠定基础。

项目成果

An RNAi screen for conserved kinases that enhance microRNA activity after dauer in Caenorhabditis elegans

• DOI: 10.1093/g3journal/jkae007
• 发表时间: 2024-02-01
• 期刊: G3-GENES GENOMES GENETICS
• 影响因子: 2.6
• 作者: Roka Pun，Himal;Karp，Xantha
• 通讯作者: Karp，Xantha

Distinct daf-16 isoforms regulate specification of vulval precursor cells in Caenorhabditis elegans.

• DOI: 10.17912/micropub.biology.000706
• 发表时间: 2022
• 期刊: microPublication biology
• 作者: Cuko, Liberta;Cale, Allison R;Rambo, Loni;Knoblock, Macy L;Karp, Xantha
• 通讯作者: Karp, Xantha