Role of Nucleolus and Ribosome Biogenesis in Coordinating Organism-wide Growth

我的研究计划的首要使命是阐明核糖体DNA（rDNA）基因座和 核糖体生物发生连接到细胞过程，以协调生物体过程中复杂的生长模式。 发展目前建议的总体目标是：（1）识别细胞非自主因素 提供核糖体合成检查点以控制生物体范围内的生长，以及（2）研究 核仁在生物体发育中的表观遗传作用。首先，我们将确定细胞非- C.自主生长停滞通过在菌株中进行密集的正向遗传筛选， 型和纯合子核糖体蛋白质和rDNA无效细胞精确的谱系。了解组织特异性 为了对整个生物体的生长做出贡献，我们将优化一个可逆地阻断新核糖体的系统， 以组织和阶段特异性的方式合成。第二，我们将利用可行的C。线虫胚胎， 缺乏多拷贝rDNA基因座（因此核仁结构）来研究核仁在 基因组组织和基因表达。我们将识别和验证核仁相关域。我们将 然后确定核仁对染色体结构、基因组组织和基因的整体影响， 表情这项研究将（1）阐明调节整个生物体的细胞非自主途径。 生长协调和（2）将确定核仁的表观遗传作用，这是不同于其基本 核糖体生物合成功能

The overarching mission of my research program is to elucidate how the ribosomal DNA (rDNA) locus and ribosome biogenesis connect to cellular processes to coordinate complex growth modes during organismal development. The overall objectives of the current proposal are: (1) identification of cell non-autonomous factors that provide a ribosome synthesis checkpoint to control organism-wide growth and (2) investigation of the epigenetic function of nucleolus during organism development. First, we will identify regulators of cell non- autonomous growth arrest in C. elegans by intensive forward genetic screens in strains that produce both wild- type and homozygous ribosomal protein & rDNA null cells in precise lineages. To understand tissue specific contributions to organism-wide growth, we will optimize a system that will reversibly block new ribosome synthesis in a tissue and stage-specific way. Second, we will take advantage of viable C. elegans embryos that lack multi-copy rDNA locus (hence the nucleolus structure) to investigate the fundamental roles of nucleolus in genome organization and gene expression. We will identify and validate nucleolus associated domains. We will then identify the global impact of nucleolus on chromosome architecture, genome organization and gene expression. This study will (1) shed light onto the cell non-autonomous pathways that regulate organism-wide growth coordination and (2) will identify the epigenetic roles of the nucleolus that are distinct from its essential ribosome biogenesis function.