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How Do Genome and Capsid Fluctuations Determine the Translation Efficiencies of RNA Viruses?

基因组和衣壳波动如何决定 RNA 病毒的翻译效率？

基本信息

批准号：
1716925
负责人：
William Gelbart
金额：
$ 76.61万
依托单位：
University of California-Los Angeles
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-15 至 2021-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1716925&HistoricalAwards=false
关键词：
How Do Genome Capsid Fluctuations

项目摘要

Many viruses, including animal and plant pathogens, have very simple genomes and life cycles, and yet little is known about how their genes start working once they have infected their host. This project studies plant virus made of a single RNA molecule packaged inside a spherical shell of protein (capsid), and this virus will be investigated using methods and techniques of molecular biology and physics. The main question that will be answered is how virus genome (which is made of RNA instead of DNA) is pulled out of the capsid inside the cell. Programs currently in place between UCLA and Historically Black Colleges and Universities (HBCU), California State University Dominguez Hills (with its 70% population of under-represented minorities), and China (through UCLA's Cross-disciplinary Students in Science and Technology [CSST] program) will enable the participation of diverse undergraduate students in research during the next three summers. The scientific aims of this research are focused on viruses whose genomes are directly translated into protein products in the cytoplasm of infected cells, as opposed to more complicated viruses whose genomes involve DNA replication and transcription and hence need to enter the nucleus of their host cells. The particular hypothesis being tested in this work is the possibility that the viral genome can engage with the ribosomal machinery and have its genes expressed even as the capsid protecting it remains intact. Several single-virus-particle methods will be used in attempts to catch an end of the genome as it fluctuates out of the intact capsid and initiates its gene expression (translation into protein products). State-of-the-art physical techniques, including high-resolution cryoelectron microscopy structure determination, and optical and magnetic "tweezers" capable of manipulating separately both the viral genome and its capsid, will be exploited throughout the project.

许多病毒，包括动物和植物病原体，都有非常简单的基因组和生命周期，但人们对它们的基因在感染宿主后如何开始工作知之甚少。本项目研究由单个RNA分子包装在蛋白质的球形壳（衣壳）内构成的植物病毒，并将使用分子生物学和物理学的方法和技术对该病毒进行研究。将要回答的主要问题是病毒基因组（由RNA而不是DNA组成）是如何从细胞内的衣壳中拉出的。加州大学洛杉矶分校和历史上的黑人学院和大学（HBCU），加州州立大学多明格斯山（其70%的人口代表不足的少数民族）和中国（通过加州大学洛杉矶分校的跨学科学生在科学和技术[CSST]计划）之间目前正在实施的计划将使不同的本科生在未来三个夏天参与研究。这项研究的科学目的是集中在病毒的基因组直接翻译成蛋白质产品在感染细胞的细胞质，而不是更复杂的病毒，其基因组涉及DNA复制和转录，因此需要进入其宿主细胞的细胞核。在这项工作中测试的特定假设是，病毒基因组可以与核糖体机器接合，并且即使保护它的衣壳保持完整，它的基因也可以表达。将使用几种单病毒颗粒方法试图捕获基因组的末端，因为它从完整的衣壳中波动出来并启动其基因表达（翻译成蛋白质产物）。在整个项目中，将利用最先进的物理技术，包括高分辨率冷冻电子显微镜结构测定，以及能够分别操纵病毒基因组及其衣壳的光学和磁性“镊子”。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Two-Stage Dynamics of In Vivo Bacteriophage Genome Ejection

DOI：
10.1103/physrevx.8.021029
发表时间：
2018-05-01
期刊：
PHYSICAL REVIEW X
影响因子：
12.5
作者：
Chen, Yi-Ju;Wu, David;Kegel, Willem K.
通讯作者：
Kegel, Willem K.

The effect of macromolecular crowding on single-round transcription by Escherichia coli RNA polymerase

DOI：
10.1093/nar/gky1277
发表时间：
2019-02-20
期刊：
NUCLEIC ACIDS RESEARCH
影响因子：
14.9
作者：
Chung, SangYoon;Lerner, Eitan;Weiss, Shimon
通讯作者：
Weiss, Shimon

RNA Homopolymers Form Higher-Curvature Virus-like Particles Than Do Normal-Composition RNAs

RNA 均聚物比正常组成的 RNA 形成更高曲率的病毒样颗粒

DOI：
10.1016/j.bpj.2019.08.012
发表时间：
2019
期刊：
Biophysical Journal
影响因子：
3.4
作者：
Thurm, Abby R.;Beren, Christian;Duran-Meza, Ana Luisa;Knobler, Charles M.;Gelbart, William M.
通讯作者：
Gelbart, William M.

Delivery of self-amplifying RNA vaccines in in vitro reconstituted virus-like particles