CAREER: The Mechanism and Genome-Wide Regulation of Genes and Transposable Elements by Epigenetically Active Small Interfering RNAs

知识价值。转座因子（te）是可移动的，可以插入基因，引起突变。为了防止这种致突变潜能，生物体进化出了抑制TEs转录的机制。最近，PI的实验室发现，当拟南芥植物中的TE转录激活时，许多TE转录本被加工成大量新的小rna，这些小rna被称为表观遗传活性小干扰rna （easiRNAs）。据推测，这些easirna负责启动活性te的沉默，以DNA甲基化的形式建立表观遗传调控，以及产生大规模的转录组变化。该项目的主要目标是探索easiRNA的生物发生是如何被触发的，并了解easiRNA产生的多种生物学功能。研究这些过程对于理解基因组如何保持完整性并在TE转录激活中存活下来，以及细胞如何识别哪些需要表达（细胞基因），哪些应该沉默（TE）至关重要。此外，easiRNA对多种细胞功能的影响可以解释一些重要的农业现象，因此了解这些机制以及哪些基因受到影响是至关重要的。更广泛的影响。本项目将支持本科生、研究生和博士后科学家的培训和指导。此外，该项目将包括两个独立的活动，旨在最好地整合PI的研究、教学和多元化推广组成部分。首先，PI目前的青年学者计划生物学增强研讨会将继续进行，该研讨会面向哥伦布市公立学校系统的七年级学生，并将其用于青年学者计划生物学实习。在这个新颖的项目中，STEM学科中未被充分代表的少数民族中学将被纳入PI？在从事实训和学习练习的同时，获得真正的生物学实验室体验，推进生物学发现。一旦实习完成，学生将自动过渡到PI的科学指导计划。该计划将扩大到包括其他pi，并将通过为代表性不足的学生提供专业的科学研究经验和扩展的指导来影响社区。第二，项目负责人将充分将本项目的研究融入高年级本科生的年度实验课程。在俄亥俄州立大学教学促进中心课程设计研究所的帮助下，项目负责人将把该项目的具体子目标整合到本科实验课程和教育中。课程实验产生的原始数据将由班级在本科研究期刊上发表，并由PI直接使用。本课程将利用分子遗传学系的教学基础设施来教授和培训本科生分子生物学，同时也激发学生对推进科学发现的兴趣。

Intellectual Merit. Transposable elements (TEs) are mobile and can insert into genes, causing mutations. To guard against this mutagenic potential, organisms have evolved mechanisms to repress transcription of TEs. Recently the PI's laboratory has discovered that when TEs are transcriptionally activated in Arabidopsis plants, many of the TE transcripts are processed into large quantities of novel small RNAs that are termed epigenetically active small interfering RNAs (easiRNAs). These easiRNAs are hypothesized to be responsible for the initiation of silencing of active TEs, the establishment of epigenetic regulation in the form of DNA methylation, as well as production of large-scale transcriptomic changes. The major goal of this project is to explore how easiRNA biogenesis is triggered and to understand the multiple biological functions of easiRNA production. Investigation of these processes is critical for understanding how the genome maintains integrity and survives TE transcriptional activation, as well as how a cell can recognize what needs to be expressed (cellular genes) from what should be silenced (TEs). Moreover, easiRNA influence on multiple cellular functions may explain some important agricultural phenomena, and therefore it is fundamental to understand these mechanisms and which genes are affected.Broader Impacts. This project will support training and mentoring of undergraduate, graduate and post-doctoral scientists. In addition, the project will include two independent activities designed to best integrate the PI's research, teaching, and diversity outreach components. First, the PI's current Young Scholars Program Biology Enhancement Workshop, which is taught to 7th grade students from the urban Columbus public school system, will be continued and leveraged to generate the Young Scholars Program Biology Internships. In this novel program middle school underrepresented minorities in STEM disciplines will be integrated into the PI?s laboratory and get real biology laboratory experience and advance biological discovery while engaged in training and learning exercises. Once the internship is completed, the student will automatically transition into a scientific mentoring program with the PI. This program will be expanded to include other PIs and will impact the community by providing a professional scientific research experience with extended mentoring to underrepresented students. Second, the PI will fully integrate the research in this project into an annual upper-division undergraduate laboratory course. With help from Course Design Institute of the Ohio State University Center for the Advancement of Teaching, the PI will integrate specific sub-aims from this project into the undergraduate laboratory curriculum and education. The original data produced from the course experiments will be published by the class in an undergraduate research journal and will be used directly by the PI. This course will leverage the Department of Molecular Genetics teaching infrastructure to teach and train undergraduate students molecular biology, while also exciting students about advancing scientific discovery.