Purine catabolites as inducers of bacterial gene expression

嘌呤分解代谢物作为细菌基因表达的诱导剂

基本信息

  • 批准号:
    2153410
  • 负责人:
  • 金额:
    $ 75.64万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-06-15 至 2025-05-31
  • 项目状态:
    未结题

项目摘要

When a bacterial pathogen infects a host, the host mounts a defense, which is intended to kill the invader. The bacteria, however, counter such defenses, often harnessing the very host-derived defense compounds to trigger changes in their own metabolism, changes that are designed to promote their survival in the inhospitable host environment. This project aims to delineate mechanisms by which bacterial plant pathogens detect and exploit host-derived signals to promote survival and virulence. A more complete understanding of the infection process will lead to novel insights into the lifecycle of economically important plant pathogens and ultimately inspire efforts to control disease progression. This program also offers an opportunity for advancing discovery while creating an inclusive training environment for students. Graduate students will be integral to developing this research project, and they will be encouraged to pursue career-building opportunities. For undergraduate students, many of whom will be recruited from institutionally established programs for minority students, a substantive research experience not only integrates with their required coursework, but it also enhances their value when entering the job market or seeking admission to professional schools. Overall, these training opportunities contribute to the development of a competitive STEM workforce.Part of the host response to pathogens is the production of reactive oxygen species. The purine catabolites urate and xanthine accumulate during infection because one of the host enzymes responsible for production of reactive oxygen species is xanthine oxidoreductase, which otherwise participates in purine metabolism by converting hypoxanthine to xanthine and xanthine to urate. Previous work has shown that PecS family transcription factors bind these purine catabolites. The primary objective of this project is to address the hypothesis that other urate/xanthine-responsive transcription factors exist. Using Burkholderia thailandensis, which encodes the PecS-family protein MftR, a combination of immunoprecipitation and mass spectrometry will be implemented to identify additional purine-responsive transcription factors. Identified proteins will be analyzed in vitro in terms of DNA and ligand binding, and in vivo experiments will include analyses of gene expression and phenotypes characteristic of strains deleted for genes encoding the identified transcription factor as well as chromatin immunoprecipitation to identify direct targets. The ability of MftR to rewire these regulatory circuits will be examined. By focusing on several proteins that respond to the same signals, the objective is to achieve a more integrated picture of the gene regulatory networks affected by purine catabolites.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.
当细菌病原体感染宿主时,宿主会进行防御,目的是杀死入侵者。然而,细菌会对抗这种防御,通常利用宿主衍生的防御化合物来触发自身代谢的变化,这些变化旨在促进它们在不适宜的宿主环境中的生存。该项目旨在描述细菌性植物病原体检测和利用宿主来源的信号来促进存活和毒性的机制。对感染过程的更全面了解将导致对经济上重要的植物病原体的生命周期的新见解,并最终激发控制疾病进展的努力。该计划还提供了一个推进发现的机会,同时为学生创造一个包容性的培训环境。研究生将是开发该研究项目不可或缺的一部分,并将鼓励他们寻求职业发展机会。对于本科生,其中许多人将从机构为少数民族学生设立的项目中招募,实质性的研究经验不仅与他们所需的课程相结合,而且还提高了他们进入就业市场或寻求进入专业学校的价值。总的来说,这些培训机会有助于培养有竞争力的STEM劳动力。宿主对病原体的部分反应是产生活性氧。在感染过程中,嘌呤的尿酸盐和黄嘌呤积累,因为负责产生活性氧的宿主酶之一是黄嘌呤氧化还原酶,其通过将次黄嘌呤转化为黄嘌呤和黄嘌呤转化为尿酸盐而参与嘌呤代谢。先前的工作已经表明,佩奇家族转录因子结合这些嘌呤催化剂。该项目的主要目的是解决存在其他尿酸盐/黄嘌呤应答转录因子的假设。使用编码PecS家族蛋白MftR的泰国伯克霍尔德氏菌,免疫沉淀和质谱的组合将被实施以识别额外的嘌呤响应性转录因子。将在体外根据DNA和配体结合分析鉴定的蛋白质,体内实验将包括分析基因表达和缺失编码鉴定的转录因子的基因的菌株的表型特征以及染色质免疫沉淀以鉴定直接靶标。将检查MftR重新连接这些调节回路的能力。通过关注对相同信号做出反应的几种蛋白质,其目标是实现受嘌呤catastrophin影响的基因调控网络的更完整的画面。该奖项反映了NSF的法定使命,并通过使用基金会的知识价值和更广泛的影响审查标准进行评估,被认为值得支持。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Anne Grove其他文献

Activity of the mammalian DNA transposon piggyBat from Myotis lucifugus is restricted by its own transposon ends
蝙蝠(Myotis lucifugus)哺乳动物 DNA 转座子 piggyBat 的活性受到其自身转座子末端的限制
  • DOI:
    10.1038/s41467-024-55784-9
  • 发表时间:
    2025-01-07
  • 期刊:
  • 影响因子:
    15.700
  • 作者:
    Alison B. Hickman;Laurie Lannes;Christopher M. Furman;Christina Hong;Lidiya Franklin;Rodolfo Ghirlando;Arpita Ghosh;Wentian Luo;Parthena Konstantinidou;Hernán A. Lorenzi;Anne Grove;Astrid D. Haase;Matthew H. Wilson;Fred Dyda
  • 通讯作者:
    Fred Dyda
Control of DNA end resection by yeast Hmo1p affects efficiency of DNA end-joining
  • DOI:
    10.1016/j.dnarep.2017.03.002
  • 发表时间:
    2017-05-01
  • 期刊:
  • 影响因子:
  • 作者:
    Arvind Panday;LiJuan Xiao;Ashish Gupta;Anne Grove
  • 通讯作者:
    Anne Grove

Anne Grove的其他文献

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{{ truncateString('Anne Grove', 18)}}的其他基金

Purine catabolites as inducers of bacterial gene expression
嘌呤分解代谢物作为细菌基因表达的诱导剂
  • 批准号:
    1714219
  • 财政年份:
    2017
  • 资助金额:
    $ 75.64万
  • 项目类别:
    Standard Grant
Evolution of Function of Bacterial PecS Family Transcription Factors
细菌PecS家族转录因子功能的进化
  • 批准号:
    1515349
  • 财政年份:
    2015
  • 资助金额:
    $ 75.64万
  • 项目类别:
    Standard Grant
Evolution of Function of Bacterial Nucleoid-Associated Proteins
细菌核相关蛋白的功能进化
  • 批准号:
    1051610
  • 财政年份:
    2011
  • 资助金额:
    $ 75.64万
  • 项目类别:
    Continuing Grant
Evolution of Function of Histone-like HU Proteins
组蛋白样 HU 蛋白的功能进化
  • 批准号:
    0414875
  • 财政年份:
    2004
  • 资助金额:
    $ 75.64万
  • 项目类别:
    Continuing Grant

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Purine catabolites as inducers of bacterial gene expression
嘌呤分解代谢物作为细菌基因表达的诱导剂
  • 批准号:
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    Standard Grant
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  • 批准号:
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