Identify 70 bp repeat-associated chromatin components by End-targeting Proteomics of Isolated Chromatin segments (PICh) and initiate their functional characterization

通过分离染色质片段 (PICh) 的末端靶向蛋白质组学鉴定 70 bp 重复相关染色质成分,并启动其功能表征

基本信息

  • 批准号:
    10293165
  • 负责人:
  • 金额:
    $ 7.43万
  • 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:
    2021-06-04 至 2023-05-31
  • 项目状态:
    已结题

项目摘要

Project Summary Trypanosoma brucei causes human African trypanosomiasis, which is frequently fatal without treatment. Few drugs are available for treating this disease, most of which have severe side-effects and are difficult to administer, while drug-resistant T. brucei infection has been on the rise. In addition, T. brucei also causes animal African trypanosomiasis, which has been a significant economic burden in sub-Sahara Africa. It is therefore important to further study T. brucei pathogenesis and identify better targets for future development of anti-parasite agents. T. brucei regularly switches its major surface antigen, VSG, to evade its mammalian host immune response. VSG switching is a major pathogenesis mechanism that enables T. brucei to establish and maintain a long-term infection. However, how VSG switching is initiated naturally in T. brucei is still not clear. T. brucei has >2,500 VSG genes and pseudogenes, all of which are located at subtelomeres. However, VSGs are expressed exclusively from subtelomeric polycistronic VSG expression sites (ESs). VSG is the last gene in any ES and within 2 kb from the telomere repeats. T. brucei has multiple ESs with very similar sequences, but only one ES is fully active at any time, resulting in a single type of VSG being expressed on the cells surface. DNA recombination has been shown to be a major pathway for VSG switching. Most VSG genes are flanked by two common sequences, which provide sequence homology for recombination between the active and a silent VSG gene in DNA recombination-mediated VSG switching events. First, all VSG 3’UTR has a common 14 nt sequences. Long telomere sequences are also found downstream of ES-linked VSGs and VSGs at minichromosome subtelomeres. Second, upstream of most VSG genes are 70 bp repeats. The 70 bp repeats in ESs can be several kb to several tens kb long. It has been shown that introducing a DNA double strand break in the 70 bp repeats immediately upstream of the active VSG gene increases the VSG switching rate for ~ 250 fold. In addition, DNA breaks are found in the 70 bp repeats in WT cells. Therefore, 70 bp repeat integrity is expected to significantly affect VSG switching frequency. However, it is unknown whether any proteins specifically associate with the 70 bp repeats, even though their sequences are highly conserved, and their associated proteins are expected to help maintain their integrity and to participate in the regulation of VSG switching. In this small project, we aim to use an improved “end-targeting proteomics of isolated chromatin segments” (ePICh) approach to isolate the 70 bp repeat chromatin and identify proteins associated with the 70 bp repeats by mass spectrometry. We will validate candidates identified in the 70 bp repeat ePICh and initiate their functional analysis. Our work will reveal clearly whether any proteins specifically associate with the 70 bp repeats, which will allow us to investigate how 70 bp repeats integrity is maintained. Our findings will open up new avenues for better understanding of the T. brucei pathogenesis and contribute to eradicate this parasite eventually.
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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Bibo Li其他文献

Bibo Li的其他文献

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{{ truncateString('Bibo Li', 18)}}的其他基金

Mechanisms of how Trypanosoma brucei TRF maintains telomere integrity
布氏锥虫 TRF 维持端粒完整性的机制
  • 批准号:
    10622535
  • 财政年份:
    2022
  • 资助金额:
    $ 7.43万
  • 项目类别:
Telomere end processing and telomere stability maintenance in trypanosomes
锥虫的端粒末端加工和端粒稳定性维持
  • 批准号:
    10503111
  • 财政年份:
    2022
  • 资助金额:
    $ 7.43万
  • 项目类别:
Mechanisms of how Trypanosoma brucei TRF maintains telomere integrity
布氏锥虫 TRF 维持端粒完整性的机制
  • 批准号:
    10526882
  • 财政年份:
    2022
  • 资助金额:
    $ 7.43万
  • 项目类别:
Telomere end processing and telomere stability maintenance in trypanosomes
锥虫的端粒末端加工和端粒稳定性维持
  • 批准号:
    10677878
  • 财政年份:
    2022
  • 资助金额:
    $ 7.43万
  • 项目类别:
Identify 70 bp repeat-associated chromatin components by End-targeting Proteomics of Isolated Chromatin segments (PICh) and initiate their functional characterization
通过分离染色质片段 (PICh) 的末端靶向蛋白质组学鉴定 70 bp 重复相关染色质成分,并启动其功能表征
  • 批准号:
    10417263
  • 财政年份:
    2021
  • 资助金额:
    $ 7.43万
  • 项目类别:
Characterization of Trypanosome telomere complex
锥虫端粒复合物的表征
  • 批准号:
    7849189
  • 财政年份:
    2009
  • 资助金额:
    $ 7.43万
  • 项目类别:
Characterization of Trypanosome telomere complex
锥虫端粒复合物的表征
  • 批准号:
    7335623
  • 财政年份:
    2007
  • 资助金额:
    $ 7.43万
  • 项目类别:
Characterization of Trypanosome telomere complex
锥虫端粒复合物的表征
  • 批准号:
    7211023
  • 财政年份:
    2007
  • 资助金额:
    $ 7.43万
  • 项目类别:
Characterize functions of T. brucei RAP1 and TRF in antigenic variation and telom
表征 T. brucei RAP1 和 TRF 在抗原变异和端粒中的功能
  • 批准号:
    8603220
  • 财政年份:
    2007
  • 资助金额:
    $ 7.43万
  • 项目类别:
Characterize functions of T. brucei RAP1 and TRF in antigenic variation and telom
表征 T. brucei RAP1 和 TRF 在抗原变异和端粒中的功能
  • 批准号:
    8107285
  • 财政年份:
    2007
  • 资助金额:
    $ 7.43万
  • 项目类别:

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