Genetic and Molecular Dissection of Meiotic Silencing by Unpaired DNA

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。该项目的总体目标是描述未配对DNA（MSUD）的减数分裂沉默机制，这是一种首次在粗糙脉孢菌中描述的新型基因沉默系统。 在染色体配对阶段，合子细胞检查整个基因组，并将任何DNA片段与其配对伴侣进行配对。 任何未与相似序列配对的基因都会产生沉默信号，随后抑制该未配对DNA以及与其同源的任何序列的基因表达，无论它们是否配对。 减数分裂沉默利用mRNA转录物的特异性破坏，一种称为RNA干扰（RNAi）的机制。 减数分裂沉默的研究将提供一个很好的模型描绘的机制，靶向未配对的DNA在减数分裂过程中沉默，这一过程可能是重要的印记X染色体失活和其他现象在高等真核生物。 由于RNAi作为揭示基因功能的实验工具具有巨大的潜力，因此对减数分裂沉默和其他基于RNA的沉默系统的理解可能对生物学所有领域的研究产生广泛的影响。 遗传学、细胞生物学和其他方法将用于鉴定减数分裂沉默系统所需的机制和机制步骤。更广泛的影响：主要研究者参与了许多教学和指导活动，如EXPRESS（暴露于科学学生的研究）计划。 为了扩大代表性不足群体的参与，本项目的研究人员将招募和培训非博士学位的本科生，资助机构和少数群体服务机构。 还将实施博士后培训计划，重点是学者准备和指导/教学技能。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).The overall goal of this project is to delineate the mechanism of Meiotic Silencing by Unpaired DNA (MSUD), a novel gene silencing system first described in Neurospora crassa. During the chromosome pairing stage, the zygotic cell examines the entire genome and compares the pairing of any DNA segment with its pairing partner. Any genes not paired with a similar sequence generates a silencing signal, which subsequently suppresses the gene expression of this unpaired DNA, as well as any sequences homologous to it, whether they are paired or not. Meiotic silencing utilizes the specific destruction of mRNA transcripts, a mechanism known as RNA interference (RNAi). The study of meiotic silencing will provide an excellent model for the delineation of the mechanism targeting unpaired DNA for silencing during meiosis, a process that could be important for imprinted X-chromosome inactivation and other phenomena in higher eukaryotes. Since RNAi has tremendous potential as an experimental tool to reveal gene functions, the understanding of meiotic silencing and other RNA-based silencing systems could have a broad impact on research in all areas of biology. Genetics, cell biology, and other approaches will be used to identify the machinery and the mechanistic steps required for the meiotic silencing system. Broader impact: The principal investigator is involved in a number of teaching and mentoring activities, such as the EXPRESS (Exposure to Research for Science Students) program. To broaden the participation of underrepresented groups, the investigators of this project will recruit and train undergraduate students from non-Ph.D.-granting and minority-serving institutions. A postdoctoral training plan with an emphasis on scholar preparation and mentoring/teaching skills will also be implemented.