Ribosomes and Growth Regulation

核糖体和生长调节

基本信息

批准号：
9160502
负责人：
Nicholas E Baker
金额：
$ 30.9万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-08 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9160502
关键词：
Affect Anabolism Aneuploid Cells Animals Cancer Etiology Cell Cycle Cell Proliferation Cell Size Cell Survival Cells Childhood Cirrhosis DNA Sequence Defect Development Diamond Diamond-Blackfan anemia Disease Drosophila genus Essential Genes Exhibits Feedback Gene Dosage Gene Expression Gene Targeting Gene-Modified Genes Genetic Genetic Transcription Genetic study Genome Genotype Growth Growth and Development function Heart Diseases Heart Hypertrophy Heterozygote Histocompatibility Testing Human Immunohistochemistry Inherited Label Lead Longevity Maintenance Malignant Neoplasms Mandibulofacial Dysostosis Maps Microscopy Modeling Molecular Genetics Mutation Neurofibromin 2 North American Indians Northern Blotting Nucleic Acid Regulatory Sequences Organ Organism Pathway interactions Process Protein Biosynthesis Regulation Resistance Resolution Ribosomal Proteins Ribosomal RNA Ribosomes Role Spleen Syndrome Testing Tissues Translations Transmission Electron Microscopy bZIP Domain base cell fixing cell growth cell type imaginal disc improved irradiation loss of function macromolecule mutant novel novel therapeutics overexpression programs reproductive transcription factor transcriptome transcriptome sequencing

项目摘要

Ribosomes are responsible for protein synthesis and therefore necessary for the growth of all organs, in both normal development and in disease conditions such as cancer or cardiac hypertrophy. A number of congenital conditions, collectively termed ribosomopathies, result from defects in components of the ribosome or affect its biosynthesis. It is unclear why ribosomopathies have such distinct effects from one another, and it is unclear why mutations in ribosomal genes can cause cancer, since they are required for growth. Reducing the number of ribosomal genes reduces growth rate but surprisingly this has been found to be mainly due to the activation of a new, previously unstudied gene that is believed to encode a transcription factor. To understand how growth is affected, the target genes of this new transcription factor will be identified using a combination of genetic and molecular genetic studies that are possible in the fruitfly. To understand how the new pathway responds to ribosomal protein gene copy number, the DNA sequences that react to such changes will be mapped and characterized. The effect of ribosomal protein gene copy changes on the number of ribosomes, and on the accumulation of their assembly intermediates will be determined to indicate how gene expression is most likely affected. To explore what advantage might accrue from a pathway that slows growth and development, the implications for cell competition, the maintenance of cell size, and for organismal longevity, resistance to genome damage, and body symmetry will be assessed. Given that ribosomes are essential components of all cells, the results of these basic studies are likely to improve understanding of growth in all organs, and diseases that affect growth including cancer, heart disease, and ribosomopathies.

核糖体负责蛋白质合成，因此对于生长来说是必要的在所有器官中，在正常发育和疾病中，例如癌症或心脏肥大。许多先天性条件，共同称为核糖体病，是由于核糖体成分缺陷或影响其核糖体病变的生物合成。目前尚不清楚核糖体病为什么与一个具有如此明显的影响另一个，尚不清楚为什么核糖体基因突变会引起癌症，因为它们是增长所必需的。减少核糖体基因的数量减少了生长速率，但令人惊讶的是，这主要是由于新的，以前未研究的基因被认为编码转录因子。到了解增长是如何影响的，该新转录因子的目标基因将可以使用遗传学和分子遗传研究的组合来鉴定在果蝇中可能。要了解新途径如何对核糖体做出反应蛋白质基因拷贝数，反应这种变化的DNA序列将是映射和特征。核糖体蛋白基因拷贝的影响对核糖体的数量，以及组装中间体的积累确定表明基因表达最有可能受到影响。探索什么优势可能会从减慢增长和发展的途径中产生对细胞竞争的影响，细胞大小的维持和有机体的影响将评估寿命，对基因组损害的抵抗力和身体对称性。给出核糖体是所有细胞的重要组成部分，这些基础研究的结果可能会提高对所有器官增长的理解，以及影响影响的疾病生长在内，包括癌症，心脏病和核糖症。