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

R环诱导染色体片段在种系中的繁殖机制

• 批准号: 2341479
• 负责人: Sarit Smolikove
• 金额: $ 55万
• 依托单位: University of Iowa
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2341479&HistoricalAwards=false
• 关键词: Mechanisms; propagation; loop; induced; chromosomal; Mechanisms; propagation; loop; induced; chromosomal

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.

遗传学的遗传学研究旨在了解遗传物质如何从一代传递到另一代。多细胞生物的繁殖需要形成卵和精子细胞。该项目将研究如何生成这些专门的细胞，重点是如何管理此过程中发生的DNA断裂。结果将有助于定义对物种传播重要的规则。该项目将包括教育活动，以提高来自不同背景的年轻K-12学生的遗传学识字能力。通过与大学生的互动以及采用游戏和创意探索方法，将向学生介绍遗传学的基本概念。这些活动将满足夏季的STEM教育的需求，而年轻的学生人群否则他们将不受科学的态度，同时为本科生提供课程开发培训。此外，该项目将为本科和研究生提供研究培训机会。PAST研究表明，卵子中的染色体断裂可能是由于RNA和DNA之间涉及长时间关联的结构的积累而导致的。破裂的染色体可以进行双链断裂修复，也可以用阻止修复的端粒序列盖住。该项目将研究后一种机制如何稳定RNA-DNA杂交引起的染色体断裂，并导致其传播到卵细胞中。 AIM 1将识别染色体修复被阻断的机制，从而导致新创建的端粒添加到染色体末端。 AIM 2将通过相同的事件刺激封盖过程，从而导致形成染色体断裂的事件。这些研究将使用细胞生物学和遗传技术在秀丽隐杆线虫模型中进行。预计这项研究将提供至关重要的见解，以对卵和精子形成具有完整和功能性染色体所需的基本生物学和遗传过程。该项目由分子和细胞生物学家划分中的分子和细胞生物学家划分的计划共同资助，并促进竞争性研究（EPSCOR）。使用基金会的智力优点和更广泛的影响评估标准进行评估。