Mechanisms for the propagation of R-loop induced chromosomal fragments in the germline

遗传学是对遗传的研究，旨在了解遗传物质是如何从一代传到下一代的。多细胞生物的繁殖需要卵细胞和精子细胞的形成。这个项目将研究这些特化细胞是如何产生的，重点是如何管理在这一过程中发生的DNA断裂。研究结果将有助于确定对物种繁殖很重要的规则。该项目将包括提高来自不同背景的年轻K-12学生的遗传学素养的教育活动。学生将通过与大学生的互动以及运用游戏和创造性探索的方法，向学生介绍遗传学的基本概念。这些活动将满足那些原本不会接触科学的年轻学生群体在夏季对STEM教育的需求，同时为本科生提供课程开发方面的培训。此外，该项目还将为本科生和研究生提供研究培训机会。过去的研究表明，卵子中的染色体断裂可能是由于RNA和DNA之间长期联系的结构的积累造成的。断裂的染色体可以进行双链断裂修复，也可以被阻止修复的端粒序列封顶。本项目将研究后一种机制如何稳定由RNA-DNA杂交体引起的染色体断裂，并导致它们传播到卵细胞。目标1将确定阻止染色体修复的机制，导致新产生的端粒增加到染色体末端。目标2将研究导致染色体断裂形成的相同事件如何刺激封顶过程。这些研究将在模式生物秀丽线虫身上进行，使用细胞生物学和基因技术。这项研究有望为形成具有完整和功能染色体的卵子和精子所需的基本生物和遗传过程提供重要的见解。该项目由分子和细胞生物科学部门的遗传机制计划和既定的刺激竞争研究计划(EPSCoR)联合资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Genetics, the study of heredity, aims to understand how genetic material is passed from one generation to the next. Reproduction of multicellular organisms requires formation of egg and sperm cells. This project will examine how these specialized cells are generated, focusing on how DNA breaks that occur during this process are managed. The outcomes will help to define rules important for the propagation of species. The project will include educational activities to improve literacy in genetics of young K-12 students from diverse backgrounds. The students will be introduced to basic concepts in genetics through interactions with university students and by applying play and creative exploration approaches. These activities will fulfill a need for STEM education during the summer for young student populations who would not otherwise be exposed to science, while providing undergraduate students with training on curriculum development. In addition, the project will provide research training opportunities for undergraduate and graduate students.Past research has shown that chromosome breaks in eggs can result from accumulation of structures involving long association between RNA and DNA. Broken chromosomes can either undergo double strand break repair or be capped with telomere sequences that block repair. This project will investigate how the latter mechanism stabilizes chromosome breaks induced by RNA-DNA hybrids and leads to their transmission into egg cells. Aim 1 will identify mechanisms by which chromosome repair is blocked, leading to addition of newly created telomeres to chromosome ends. Aim 2 will examine how the capping process is stimulated by the same events that lead to formation of chromosome breaks. The studies will be performed in the model organism Caenorhabditis elegans using cell biology and genetic techniques. The research is expected to provide crucial insights into fundamental biological and genetic processes required for the formation of eggs and sperm with intact and functional chromosomes.This project is jointly funded by the Genetic Mechanisms program in the Division of Molecular and Cellular Biosciences and the Established Program to Stimulate Competitive Research (EPSCoR).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.