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EAGER: Plant pathogenic Streptomyces encode components for genetic code mistranslation

EAGER：植物致病性链霉菌编码遗传密码误译成分

基本信息

批准号：
2304710
负责人：
Oscar Vargas-Rodriguez
金额：
$ 30万
依托单位：
University of Connecticut Health Center
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2022
资助国家：
美国
起止时间：
2022-10-01 至 2024-02-29
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2304710&HistoricalAwards=false
关键词：
EAGER Plant pathogenic Streptomyces encode

项目摘要

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117- 2). Plant-pathogenic microorganisms are ubiquitous in soils across the U.S. and negatively affect the production of vital food crops and the country’s agricultural economy. Understanding the biological mechanisms to infect and colonize plants employed by these microbes is fundamental for the development of effective management approaches. The present project will investigate novel protein factors that are uniquely encoded by a group of plant-associated microbes, including several pathogens responsible for the common scab disease in potatoes and other tubers. Early research indicates that the protein factors endow these pathogens with the ability to deliberately alter their genomic information without changing their DNA, and ultimately can result in the production of multiple protein mutants from a single gene. Why these pathogens encode these dedicated factors and how they function is largely unknown. The goals of this project are to determine the function of these factors and to explore their role in plant pathogenicity of their host species. Importantly, the implementation of this work will involve the training of two postbaccalaureate associates from underrepresented groups in STEM and will offer opportunities for undergraduate students to gain a first-hand research experience.The genetic code assigns each of the twenty canonical amino acids to one of the 61 sense codons. One of the only two exceptions to the rule of one codon specifying one amino acid was recently discovered in a small group of plant pathogens from the bacterial Streptomyces family, including Streptomyces turgidiscabies and Streptomyces scabiei. These organisms, which are the causative agents of distinct tuber diseases that cause substantial economic losses to U.S. farmers, encode an anomalous aminoacyl-tRNA synthetase and a corresponding tRNA. Expression of these factors causes translation of alanine codons as proline. This dual use of alanine codons enables the diversification and expansion of the host’s proteome due to stochastic Ala→Pro mutations, which can generate a multiplicity of protein variants from a single gene. This may provide a rapid response against stress and environmental changes as well as a mechanism for virulence and infection. This project will combine biochemical, biophysical, multi-omics, comparative genomics, genetics, and molecular biology approaches to elucidate the molecular interactions and features that enabled the emergence of these translation factors and to explore their biological function in the pathogenic Streptomyces hosts.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该奖项全部或部分根据2021年美国救援计划法案（公法117- 2）资助。植物病原微生物在美国各地的土壤中无处不在，对重要粮食作物的生产和国家的农业经济产生负面影响。了解这些微生物感染和定殖植物的生物学机制是开发有效管理方法的基础。本项目将研究由一组植物相关微生物独特编码的新型蛋白质因子，包括几种导致马铃薯和其他块茎中常见疮痂病的病原体。早期的研究表明，蛋白质因子赋予这些病原体在不改变其DNA的情况下故意改变其基因组信息的能力，并最终导致从单个基因产生多个蛋白质突变体。为什么这些病原体编码这些专用因子以及它们如何发挥作用在很大程度上是未知的。本项目的目标是确定这些因子的功能，并探讨它们在植物致病性中的作用。重要的是，这项工作的实施将涉及两名来自STEM领域代表性不足的研究生的培训，并将为本科生提供获得第一手研究经验的机会。遗传密码将20种典型氨基酸中的每一种分配给61种有义密码子中的一种。一个密码子指定一个氨基酸的规则仅有的两个例外之一最近在一小群来自细菌链霉菌家族的植物病原体中发现，包括Streptomyces turgidiscabies和Streptomyces scabiei。这些生物体是导致美国农民遭受重大经济损失的不同块茎疾病的病原体，它们编码异常氨酰-tRNA合成酶和相应的tRNA。这些因子的表达导致丙氨酸密码子翻译为脯氨酸。丙氨酸密码子的这种双重使用使得宿主蛋白质组由于随机Ala→Pro突变而多样化和扩增，这可以从单个基因产生多种蛋白质变体。这可能提供对压力和环境变化的快速反应以及毒力和感染的机制。该项目将结合联合收割机生物化学，生物物理，多组学，比较基因组学，遗传学，该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的评估来支持。影响审查标准。