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绘无配对DNA减数分裂沉默(MSUD)的机制，这是一种首次在粗脉孢子菌中描述的新的基因沉默系统。在染色体配对阶段，合子细胞检查整个基因组，并将任何DNA片段的配对与其配对伙伴进行比较。任何不与相似序列配对的基因都会产生沉默信号，从而抑制这种未配对DNA的基因表达，以及任何与之同源的序列，无论它们是否配对。减数分裂沉默利用了对mRNA转录本的特异性破坏，这一机制被称为RNA干扰(RNAi)。减数分裂沉默的研究将为描述在减数分裂过程中靶向未配对DNA沉默的机制提供一个很好的模型，这一过程可能对印记X染色体失活和高等真核生物中的其他现象起重要作用。由于RNAi作为揭示基因功能的实验工具具有巨大的潜力，对减数分裂沉默和其他基于RNA的沉默系统的理解可能会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被用来确定减数分裂沉默系统所需的机械和机械步骤。更广泛的影响：首席调查员参与了许多教学和指导活动，如EXPRESS(为理科学生接触研究)计划。为了扩大代表不足的群体的参与，该项目的调查人员将从非授予博士学位的机构和为少数群体服务的机构中招募和培训本科生。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.