Generation of DNA memory by bacterial CRISPR-Cas9 systems

通过细菌 CRISPR-Cas9 系统生成 DNA 记忆

基本信息

  • 批准号:
    10664972
  • 负责人:
  • 金额:
    $ 37.8万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-08-01 至 2025-07-31
  • 项目状态:
    未结题

项目摘要

Project Summary Prokaryotic horizontal gene transfer (HGT) underlines the spread of antibiotic resistance and pathogenic traits. The battle against antibiotic resistance must be fought on multiple fronts, including the understanding of natural barriers that microbes use to restrict HGT. Most bacteria rely on the CRISPR-Cas system to establish adaptive immunity against mobile genetic elements. DNA pieces from these invaders' genome can be captured and stored as immunological memories termed spacers, at the CRISPR loci. Small, antisense RNAs produced from CRISPR (crRNAs) will guide Cas enzymes to destroy invaders with a matching target site. In the past decade, much progress has been made in understanding the CRISPR interference enzymes and their applications in genetic engineering. However, how microbes acquire their CRISPR memories remains very poorly understood. In this proposal, we aim to uncover the molecular basis for CRISPR memorization (i.e. spacer adaptation). We use the gram-negative pathogen Neisseria meningitidis (Nme) as a model organism, due to of its clinical importance and tractable genetics. Current knowledge about spacer adaptation mostly comes from studies of the type I CRISPR native to E. coli; products of its conserved cas1-cas2 integrase genes can create functional memories independently of the interference enzymes. Our recent preliminary findings suggest that the type II CRISPR of N. meningitidis creates memory by a distinct mechanism. The interference genes, Nmecas9 and tracrRNA co-factor, play important but non-conventional roles in the acquisition of functional spacers. We will use molecular genetic, genomic and biochemical approaches to address fundamental questions, including: What are the molecular roles of Cas9 and the CRISPR-encoded tracrRNA in spacer acquisition? What are the rules governing memory DNA selection? How does Cas9/tracr cooperate with the Cas1-2 integrase? And finally, how would the anti-CRISPR proteins affect the memorization process? The proposed research will illuminate the interplay between pathogenic bacteria, their CRISPR systems, and HGT. This work also promises to guide technology advances, including CRISPR-based novel antimicrobials that kill specific bacterial pathogens, and Cas9-Cas1-Cas2 based genome-tagging devices that help record cellular/disease history.
项目总结

项目成果

期刊论文数量(0)
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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Yan Zhang其他文献

Yan Zhang的其他文献

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{{ truncateString('Yan Zhang', 18)}}的其他基金

The stage-specific regulation of ameloblastin and enamelin by the distinct nuclear factors
不同核因子对成釉素和釉质的阶段特异性调节
  • 批准号:
    10804126
  • 财政年份:
    2023
  • 资助金额:
    $ 37.8万
  • 项目类别:
High Urinary Phosphate Induces TLR4-mediated Inflammation and Cystogenesis in Polycystic Kidney Disease
高尿磷酸盐诱导多囊肾病中 TLR4 介导的炎症和囊肿发生
  • 批准号:
    10730615
  • 财政年份:
    2023
  • 资助金额:
    $ 37.8万
  • 项目类别:
The stage-specific regulation of ameloblastin and enamelin by the distinct nuclear factors
不同核因子对成釉素和釉质的阶段特异性调节
  • 批准号:
    10645781
  • 财政年份:
    2022
  • 资助金额:
    $ 37.8万
  • 项目类别:
Generation of DNA memory by bacterial CRISPR-Cas9 systems
通过细菌 CRISPR-Cas9 系统生成 DNA 记忆
  • 批准号:
    10454868
  • 财政年份:
    2020
  • 资助金额:
    $ 37.8万
  • 项目类别:
Generation of DNA memory by bacterial CRISPR-Cas9 systems
通过细菌 CRISPR-Cas9 系统生成 DNA 记忆
  • 批准号:
    10026656
  • 财政年份:
    2020
  • 资助金额:
    $ 37.8万
  • 项目类别:
Generation of DNA memory by bacterial CRISPR-Cas9 systems
通过细菌 CRISPR-Cas9 系统生成 DNA 记忆
  • 批准号:
    10792662
  • 财政年份:
    2020
  • 资助金额:
    $ 37.8万
  • 项目类别:
Generation of DNA memory by bacterial CRISPR-Cas9 systems
通过细菌 CRISPR-Cas9 系统生成 DNA 记忆
  • 批准号:
    10227166
  • 财政年份:
    2020
  • 资助金额:
    $ 37.8万
  • 项目类别:
Investigating the Role of BACE2 in Melanocyte Development and Melanoma Progression
研究 BACE2 在黑色素细胞发育和黑色素瘤进展中的作用
  • 批准号:
    9814738
  • 财政年份:
    2019
  • 资助金额:
    $ 37.8万
  • 项目类别:
Regulation of enamel matrix protein secretion in ameloblasts
成釉细胞釉质基质蛋白分泌的调节
  • 批准号:
    10192703
  • 财政年份:
    2017
  • 资助金额:
    $ 37.8万
  • 项目类别:
Investigating the Role of BACE2 in Melanocyte Development and Melanoma Progression
研究 BACE2 在黑色素细胞发育和黑色素瘤进展中的作用
  • 批准号:
    9229644
  • 财政年份:
    2016
  • 资助金额:
    $ 37.8万
  • 项目类别:

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