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

非技术描述：在自然界中，动物生长在不同且经常变化的环境中。恶劣的环境，如寒冷的天气或食物不足，会导致动物的生长速度减慢，甚至完全停止生长。尽管这种严重的中断对他们的发展，如果环境改善，动物将继续他们的成长，并最终成为正常的成年人。让动物在长时间中断后正常发育的基因和蛋白质是未知的，这是一个主要的知识空白。该项目建立在PI先前的工作基础上，在微观线虫C. elegans中研究这个问题。这些蠕虫是一个有价值的模型，因为它们简单，易于实验使用。此外，秀丽隐杆线虫与人类共有7663个基因，这意味着我们从秀丽隐杆线虫中学到的东西通常是跨物种相关的。作为这项研究的一部分，一个新项目将让实习教师参与研究。该项目将培养教师领袖，他们将在K-12阶段提供有效的STEM教育。这种教育对于美国保持其在科学领域的领导地位，以及为学生提供雇主看重的技能至关重要。此外，这项研究将导致许多本科生和研究生在PI的研究实验室和PI教授的实验课程中得到培训。技术描述：拟作的工作利用秀丽隐杆线虫的力量作为模型来阐明使发育在滞育后正常发生的机制。在良好的环境下，秀丽隐杆线虫通过四个幼虫期连续发育，以蜕皮为间隔。相反，不利的环境会促使幼虫在发育的中途进入滞育（“滞育”）。尽管这种中断，如果再次遇到有利条件，由于发育途径的调节和细胞命运的重新设置，发育正常进行。PI先前的工作表明，microRNA活性的增强是后发发育程序的关键组成部分。本项目建立在这项工作的基础上，以发现和表征涉及后涂抹microRNA途径的因素。初步数据表明，ZTF-16和FOXO/DAF-16这两种转录因子在死亡后通路中起着重要作用。遗传学和分子实验将验证ZTF-16是microRNA靶点的假设和FOXO/DAF-16是microRNA活性调节剂的假设。此外，基因组方法将确定使适当的后发发育成为可能的因素。完成该项目将明确控制细胞命运的microRNA通路在洪水后被调节的机制，并为未来的工作奠定基础。

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.