中文摘要
在老龄化问题日趋严峻的今天,衰老以及衰老相关疾病的研究具有重要的科学价值和社会意义。衰老是伴随个体年龄增长而表现出的多器官的渐进性功能退行,这些衰退往往和机体的蛋白质网络功能失调相关。基于高通量质谱的蛋白质组学技术可以对成千上万的蛋白质进行精确表征,使其成为衰老生物学研究的必要手段。已有的衰老蛋白质组研究多聚焦于蛋白质的表达变化,但蛋白质功能失调可能和蛋白质的多种特性相关,例如蛋白质修饰、蛋白聚集体、蛋白质稳态及降解等。本研究采用经典的果蝇衰老模型为研究对象,揭示衰老过程中多器官的蛋白质表达、蛋白质聚集、长寿蛋白、蛋白质泛素化修饰、蛋白质翻译速率等的变化,结合业已产生的基因组转录本表达数据,系统阐释衰老过程中的蛋白质组的多维变化。其中,针对蛋白质翻译及线粒体的深度研究有望对其调控衰老的作用提出机制上的解释。
英文摘要
A rapidly increasing proportion of aging population has become a major social and economic problem in China today. Thus, understanding the process of aging and aging related diseases is particularly important. The aging-related functional decline of multiple organs often involves the dysfunction of protein molecules and the network they compose. In recent years, mass spectrometry-based proteomics has emerged as a high throughput tool to accurately characterize thousands of proteins of the whole proteome. This proposal will use mass spectrometry-based proteomics to study the mechanism of aging at the level of proteome. Previous aging studies using proteomic methods often focused on one aspect of proteins, but the protein dysfunction during aging may be associated with a variety of properties of proteins, such as protein modification, protein aggregates, etc. This proposed study will use Drosophila as a model organism to study proteomes in multiple dimensions during aging process, including protein abundance, protein aggregation, long-lived proteins, protein ubiquitination, and protein translation rate, etc., and compare such as with RNAseq data which has been generated. This project will seek to understand the dynamic changes at the level of proteome during aging process of Drosophila. With the existing genetic tools in Drosophila as a model organism, we expect this study will provide powerful new insights into the mechanisms of protein translation and mitochondrial proteins in the regulation of aging.
