Noncanonical functions of the ribosome in response to cellular stress

核糖体响应细胞应激的非常规功能

• 批准号: 10926463
• 负责人: Colin Wu
• 金额: $ 134.95万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10926463
• 关键词: Apoptotic; Biochemical; CRISPR screen; Cell Death Induction; Cells; Cellular Stress; Cessation of life; Chemicals; Computing Methodologies; Cues; Data; Distress; Gene Expression; Goals; Health; Human; Hypoxia; Laboratories; Life; Mass Spectrum Analysis; Messenger RNA; Modification; Molecular; Monitor; Nutrient; Output; RNA; Research; Ribosomes; Starvation; Stress; Techniques; Technology; Translational Regulation; Work; genome-wide; member; nanopore; novel; programs; response; ribosome profiling; ultraviolet irradiation

My laboratory broadly investigates the function of the ribosome in determining cell fate decisions. Some work began soon after the launch of the lab in late 2020, the setup of the laboratory space was accomplished, and section members were hired. Research in the lab has focused on how ribosomes sense and respond to translational distress induced by cellular or environmental stress conditions, such as nutrient starvation, hypoxia, and UV irradiation. Cellular stress influences how ribosomes move along the mRNA templates, therefore changing the translational landscape and ultimately altering the gene expression programs of the cell. A better understanding of the mechanism of translational regulation under stress conditions is therefore essential for overcoming challenges to human health. We have begun deciphering the molecular mechanisms of cell death induced by damaged RNA. We have adapted Nanopore RNA direct sequencing technology to monitor RNA damage and modification caused by cellular and environmental stress, and we are currently developing computational methods for analyzing Nanopore sequencing data from stressed cells.

我的实验室广泛地研究了核糖体在决定细胞命运方面的功能。实验室于2020年底启动后不久便开始了一些工作，实验室空间的设置已经完成，并聘请了部门成员。实验室的研究主要集中在核糖体如何感知和响应细胞或环境应激条件（如营养饥饿，缺氧和紫外线照射）引起的翻译窘迫。细胞应激影响核糖体如何沿着mRNA模板沿着移动，从而改变翻译景观并最终改变细胞的基因表达程序。因此，更好地了解应激条件下的翻译调控机制对于克服人类健康面临的挑战至关重要。我们已经开始破译受损RNA诱导细胞死亡的分子机制。我们已经采用了Nanopore RNA直接测序技术来监测由细胞和环境应激引起的RNA损伤和修饰，我们目前正在开发用于分析应激细胞的Nanopore测序数据的计算方法。

项目成果

High-Resolution Ribosome Profiling for Determining Ribosome Functional States During Translation Elongation.

用于确定翻译延伸过程中核糖体功能状态的高分辨率核糖体分析。

• DOI: 10.1007/978-1-0716-1975-9_11
• 发表时间: 2022
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Shafieinouri,Mohammad;Membreno,BritnieSantiago;Wu,ColinChih-Chien
• 通讯作者: Wu,ColinChih-Chien