CRISPR interference-enabled phenotyping of essential genes in C. difficile to aid in discovery of antibiotic targets

对艰难梭菌中的必需基因进行 CRISPR 干扰表型分析,以帮助发现抗生素靶标

基本信息

  • 批准号:
    10518406
  • 负责人:
  • 金额:
    $ 17.38万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-11-02 至 2024-10-31
  • 项目状态:
    已结题

项目摘要

Project Summary Clostridioides (Clostridium) difficile infections strike close to 500,000 people a year in the United States, leading to nearly 30,000 deaths. The CDC has declared this organism an “urgent” threat to public health, the highest threat category. New treatments are sorely needed. Most antibiotics inhibit proteins that are essential for viability, so a better understanding of these proteins and the genes that encode them can advance efforts to develop new antibiotics. Although essential genes are difficult to study, new techniques for manipulating bacterial gene expression are overcoming this barrier. One emerging technology for studying essential genes in bacteria is called CRISPR interference (CRISPRi). CRISPRi uses a short RNA to guide a protein called dCas9 to a gene, thereby creating a roadblock that prevents RNA polymerase from transcribing that gene. CRISPRi is well-suited for screening large sets of genes because repressing a new target is simply a matter of cloning a synthetic DNA sequence encoding the right guide RNA into the plasmid, a process that is easily scaled-up. Another key feature of our CRISPRi system is that dCas9 is expressed from a xylose-inducible promoter, which allows us to control the timing and extent of gene repression. The specific objective of this proposal is to deploy CRISPRi to characterize 187 putatively essential genes in C. difficile. In Aim 1 we will construct a CRISPRi library and use it to vet the essentiality of the genes on our target list. In Aim 2 we will determine whether gene knockdown results in morphological defects or increases sensitivity to a panel of antibiotics chosen to target a variety of cellular processes. The information from these assays will enable us to assign many of these genes to functional pathways. It will also provide foundational knowledge and tools for developing new antibiotics to treat C. difficile infections.
项目总结

项目成果

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{{ truncateString('DAVID S WEISS', 18)}}的其他基金

Heteroresistance Interdisciplinary Research Unit (Project 2)
异阻性跨学科研究单元(项目2)
  • 批准号:
    10366038
  • 财政年份:
    2021
  • 资助金额:
    $ 17.38万
  • 项目类别:
CRISPR interference-enabled phenotyping of essential genes in C. difficile to aid in discovery of antibiotic targets
对艰难梭菌中的必需基因进行 CRISPR 干扰表型分析,以帮助发现抗生素靶标
  • 批准号:
    10369416
  • 财政年份:
    2021
  • 资助金额:
    $ 17.38万
  • 项目类别:
Heteroresistance Interdisciplinary Research Unit (Project 2)
异阻性跨学科研究单元(项目2)
  • 批准号:
    10583505
  • 财政年份:
    2021
  • 资助金额:
    $ 17.38万
  • 项目类别:
Heteroresistance Interdisciplinary Research Unit (Project 2)
异阻性跨学科研究单元(项目2)
  • 批准号:
    10170971
  • 财政年份:
    2021
  • 资助金额:
    $ 17.38万
  • 项目类别:
Heteroresistance Interdisciplinary Research Unit (Admin Core)
异阻性跨学科研究单位(行政核心)
  • 批准号:
    10170967
  • 财政年份:
    2021
  • 资助金额:
    $ 17.38万
  • 项目类别:
Heteroresistance Interdisciplinary Research Unit (Admin Core)
异阻性跨学科研究单位(行政核心)
  • 批准号:
    10583498
  • 财政年份:
    2021
  • 资助金额:
    $ 17.38万
  • 项目类别:
Heteroresistance Interdisciplinary Research Unit (Admin Core)
异阻性跨学科研究单位(行政核心)
  • 批准号:
    10366034
  • 财政年份:
    2021
  • 资助金额:
    $ 17.38万
  • 项目类别:
Exploitation of multiple heteroresistance for effective antibiotic combination therapy
利用多重异质耐药性进行有效的抗生素联合治疗
  • 批准号:
    10646392
  • 财政年份:
    2020
  • 资助金额:
    $ 17.38万
  • 项目类别:
Exploitation of multiple heteroresistance for effective antibiotic combination therapy
利用多重异质耐药性进行有效的抗生素联合治疗
  • 批准号:
    10206015
  • 财政年份:
    2020
  • 资助金额:
    $ 17.38万
  • 项目类别:
Exploitation of multiple heteroresistance for effective antibiotic combination therapy
利用多重异质耐药性进行有效的抗生素联合治疗
  • 批准号:
    10053046
  • 财政年份:
    2020
  • 资助金额:
    $ 17.38万
  • 项目类别:

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