Ribosomes and growth regulation.

核糖体负责细胞中的蛋白质合成，并且是细胞生长和细胞增殖所必需的。 师.干扰核糖体生物合成的遗传缺陷会减少翻译和生长 导致人类疾病许多核糖体蛋白基因的杂合突变导致 Diamond-Blackfan贫血，与早发性贫血、形态缺陷、 和癌症易感性。核糖体蛋白基因在果蝇中也是单倍不足的 果蝇，它们会导致蛋白质合成减少，生长和发育缓慢， 形态缺陷出乎意料的是，发现这些效应具有转录基础， 核糖体蛋白突变激活了一种控制翻译的转录程序， 其他影响。该项目将确定核糖体生物合成缺陷如何导致人类 通过阐明这种转录反应的分子机制， 果蝇，并利用突变，防止细胞反应的核糖体蛋白质突变。 该项目将使用核糖体分析方法来定义步骤的层次结构， 基因组向蛋白质的翻译被改变，并突出那些可能与 癌症贫血和形态学该项目将使用基因修饰方法来定义 单个蛋白质异构体和结构域在核糖体作用中的特定作用 生物成因缺陷该项目将探讨什么样的生理和选择性的作用， 细胞对核糖体生物合成缺陷的反应，以及它们对促进健康的贡献 生存和预防疾病。预计这些发现将为以下方面提出建议： 预防癌症和治疗核糖体病钻石黑帆贫血。

Ribosomes are responsible for protein synthesis in the cell and are essential for growth and cell division. Genetic defects that interfere with ribosome biogenesis reduce translation and growth and cause human diseases. Heterozygous mutation of many ribosomal protein genes causes Diamond-Blackfan Anemia, which is associated with early onset anemia, morphological defects, and cancer predisposition. Ribosomal protein genes are also haploinsufficient in the fruitfly Drosophila, where they cause reduced protein synthesis, slow growth and development, and morphological defects. Unexpectedly, these effects are found to have a transcriptional basis, that is, ribosomal protein mutations activate a transcriptional program which controls translation and the other effects. This project will determine how ribosome biogenesis defects cause human diseases and cancer by elucidating the molecular mechanisms of this transcriptional response in Drosophila, and exploiting mutations that prevent cells reacting to ribosomal protein mutations. The project will use ribosome profiling methods to define the hierarchy of steps at which translation of the genome into protein is altered and highlight those likely to be relevant to cancer, anemia, and morphology. The project will use gene modification approaches to define the specific roles of individual protein isoforms and domains in the effects of ribosome biogenesis defects. The project will explore what physiological and selective role is played by the cellular responses to ribosome biogenesis defects, and their contribution to promoting health and survival and preventing disease. The findings are anticipated to suggest approaches to prevent cancer and treat the ribosomopathy Diamond Blackfan Anemia.