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

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.

遗传学是研究遗传的学科，旨在了解遗传物质是如何从一代传递到下一代的。多细胞生物的繁殖需要卵细胞和精细胞的形成。该项目将研究这些特化细胞是如何产生的，重点是如何管理在此过程中发生的DNA断裂。这些结果将有助于确定对物种繁殖很重要的规则。该项目将包括教育活动，以提高来自不同背景的年轻K-12学生的遗传学知识。学生将通过与大学生的互动，并通过应用游戏和创造性的探索方法，介绍遗传学的基本概念。这些活动将满足夏季对STEM教育的需求，为那些无法接触科学的年轻学生提供教育，同时为本科生提供课程开发培训。过去的研究表明，卵子中的染色体断裂可能是由于RNA和DNA之间的长期关联结构积累所致。断裂的染色体可以进行双链断裂修复，也可以被端粒序列覆盖，从而阻止修复。本项目将研究后一种机制如何稳定RNA-DNA杂交诱导的染色体断裂，并导致其传递到卵细胞中。目的1将确定染色体修复被阻断的机制，导致新产生的端粒添加到染色体末端。目的2将研究如何加帽过程是由相同的事件，导致染色体断裂的形成刺激。这些研究将使用细胞生物学和遗传技术在模式生物秀丽隐杆线虫中进行。该研究将为人类形成具有完整和功能性染色体的卵子和精子所需的基本生物学和遗传学过程提供重要见解。该项目由分子和细胞生物科学部的遗传机制计划和刺激竞争研究的既定计划（EPSCoR）共同资助该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。