Proteome reprogramming by tRNA-cleaving toxins

通过 tRNA 裂解毒素进行蛋白质组重编程

基本信息

批准号：
10112828
负责人：
NANCY ANN WOYCHIK
金额：
$ 18.68万
依托单位：
RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-02-21 至 2023-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10112828
关键词：
AIDS/HIV problem Bacteria Biological Assay Cause of Death Cell physiology Cells Cessation of life Characteristics Chimera organism Chimeric Proteins Cleaved cell Codon Nucleotides Cysteine-Specific tRNA Data Data Set Disease Event Exhibits Fos-Related Antigens Growth HIV Human Immune Immune response Immune system In Vitro Infection LacZ Genes Mass Spectrum Analysis Mediating Metabolism Molecular Mycobacterium tuberculosis Operative Surgical Procedures Organism Physiology Proteins Proteome RNA Recombinants Regimen Reporter Ribosomal Frameshifting Ribosomes Sea Specificity Stress System Testing Therapeutic Time Toxin Transfer RNA Translations Tuberculosis Validation alpha Toxin antimicrobial antitoxin assault beta-Galactosidase cell growth comparative experimental study genome-wide in vivo latent infection leucylmethionine novel pathogen response transcriptome transcriptome sequencing

项目摘要

Project Summary Mycobacterium tuberculosis (Mtb) has adapted to survive a wide range of assaults—from our immune response to antimicrobial therapeutics—intended to eradicate the organism. However, the molecular switches that enable Mtb to endure these stresses, to slow replication or to become dormant as a latent tuberculosis infection are not known. Emerging studies on the molecular underpinnings of stress survival point to the activity of the toxin component of Mtb toxin-antitoxin systems in mediating the switch to the non-replicating persistent state characteristic of latent tuberculosis infection. This R21 proposal outlines experiments that test the novel hypothesis that a subset of these toxins do not globally inhibit translation but instead are highly specific tRNases that trigger a combination of ribosome frameshifting and ribosome stalling to surgically manipulate the Mtb proteome as a means to alter the physiology and/or metabolism of this pathogen.

项目摘要结核分枝杆菌（MTB）已经适应了广泛的攻击，从我们的免疫冲突中对于抗菌理论 - 旨在放射性生物体。但是，启用的分子开关 MTB忍受这些应力，缓慢复制或因潜在结核病感染而休眠已知。关于应激存活的分子基础的新兴研究表明毒素的活性 MTB毒素 - 抗毒素系统的组成部分，将转换为非复制持续状态的切换潜在结核病感染的特征。该R21提案概述了测试新颖的实验假设这些毒素的子集不抑制全球翻译，而是高度特定的TRNass 这会触发核糖体帧丝膜和核糖体停滞以手术操纵MTB的组合蛋白质组作为改变这种病原体的生理和/或代谢的一种手段。