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.

该奖项是根据2021年《美国救援计划法》（公法117-2）全部或部分资助的。植物病原性微生物在美国各地的土壤中无处不在，并对重要的粮食作物和该国的农业经济产生负面影响。了解这些微生物采用的感染和定居植物的生物学机制对于开发有效的管理方法至关重要。本项目将研究由一组植物相关的微生物唯一编码的新型蛋白质因子，其中包括几种负责土豆和其他块茎中常见scab病的病原体。早期研究表明，蛋白质因子赋予了这些病原体的能力，可以故意改变其基因组信息而不改变其DNA，最终可能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门的因素及其功能如何在很大程度上未知。该项目的目标是确定这些因素的功能，并探索它们在宿主物种的植物致病性中的作用。重要的是，这项工作的实施将涉及培训STEM中代表性不足的团体的两名后库后同伴的培训，并将为本科生提供获得第一手研究经验的机会。该遗传密码分配了20个典型的氨基酸中的每一个，将其分配给61个感觉密码子之一。最近在细菌链霉菌家族的一小群植物病原体中发现了一个密码子规则的仅有的两个例外之一，包括链球菌thepomyces turgidiscabies和scabiei。这些生物是对美国农民造成大量经济损失的严重块茎疾病的严重药物，编码了一种异常的氨基酰基-TRNA合成酶和相应的tRNA。这些因素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宿主的蛋白质组的多样化和扩展是由于随机ALA→Pro突变，从而可以产生来自单个基因的蛋白质变体。这可能会为压力和环境变化以及病毒和感染的机制提供快速的反应。 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 precious of support through evaluation using the Foundation's intellectual merit and broader影响审查标准。