Genetic and Molecular Dissection of Meiotic Silencing by Unpaired DNA

在许多生物体中，存在基因组监视系统来控制病毒和其他自私DNA元素的基因表达和传播。本项目的目的是阐明一种被称为非配对DNA减数分裂沉默（MSUD）现象的潜在机制，这是橙面包霉菌神经孢子虫的基因沉默系统。在这个系统中，细胞在繁殖过程中检查与其伴侣的基因配对；任何存在于亲本染色体一方而不存在于另一方的基因都是失活的。作为获得诺贝尔奖的“一基因一酶假说”背后的真菌，N. crassa由于其广泛的突变选择，全基因组序列的可用性以及基因沉默研究的悠久历史，是研究MSUD的理想生物。与真菌一样，蠕虫、小鼠和人类的DNA在发育过程中缺乏配对伙伴，也是沉默的目标。MSUD的研究将为非配对DNA在真菌和高等生物基因沉默中的作用提供有价值的见解。本研究的目的是表征MSUD的突变缺陷，并检查对这一过程重要的基因。更广泛的影响：为了扩大代表性不足的群体的参与，该项目的研究人员将从他们自己的大学和其他非博士中招募和培训本科生。-资助和少数族裔服务机构（通过各种校园和国家科学基金会多元化项目）。这项工作的研究活动将用于为各种外展项目制定课程计划。还将努力促进科学素养和跨学科伙伴关系。

In many organisms, genome surveillance systems are present to control the gene expression and spread of viruses and other selfish DNA elements. The goal of this project is to elucidate the underlying mechanism of a phenomenon termed Meiotic Silencing by Unpaired DNA (MSUD), a gene silencing system in the orange bread mold Neurospora crassa. In this system, the cell examines the pairing of genes with their partners during reproduction; any gene that is present in one parental chromosome but not the other is inactivated. As the fungus behind the Nobel Prize-winning "one gene-one enzyme hypothesis", N. crassa is an ideal organism for studying MSUD due to its wide mutant selections, the availability of its full genome sequence, and its long history of gene silencing research. As with fungi, DNA lacking a pairing partner in worms, mice, and humans are also targeted for silencing during development. The study of MSUD will provide valuable insights into the role of unpaired DNA in gene silencing in fungi and higher organisms. The objectives of this research are to characterize mutants defective in MSUD and examine genes that are important for this process.Broader impact: To broaden the participation of underrepresented groups, the investigators of this project will recruit and train undergraduate students from their own university as well as from other non-Ph.D.-granting and minority-serving institutions (through a variety of campus and NSF diversity programs). Research activities from this work will be used to develop lesson plans for various outreach projects. Efforts will also be made to promote scientific literacy and interdisciplinary partnership.