Regulatory circuitry controlling the cell cycle of Helicobacter pylori

控制幽门螺杆菌细胞周期的调节电路

基本信息

  • 批准号:
    9207987
  • 负责人:
  • 金额:
    $ 14.8万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-09-01 至 2020-08-31
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract There is a fundamental gap in our understanding of how helicobacter pylori (Hp), a bacterium that is highly relevant to public health, regulates its life cycle. Although mechanistic details of how Hp induces damage to host cells have been revealed, our understanding for how this pathogen regulates its own proliferation remains unclear. The existence of this knowledge gap represents a burden in the need to develop novel specie-specific drugs that can control the proliferation of Hp in human patients. Our long-term goal is to identify drug targets that are essential in regulating Hp cell cycle and proliferation. The overall objective of the proposed research is to define the regulatory circuitry that controls the forward progression of Hp cell cycle. Our central hypothesis is that the chromosome replication initiator DnaA in Hp is a central node connecting multiple cell cycle regulating factors. DnaA is a multifunctional protein that aside from opening the chromosomal region known as the origin of replication (ori), it also acts as a highly regulated transcription factor. The rationale for the proposed research is that DNA replication initiators have been shown to influence the activity of other cellular machines involved in the cell cycle, such as cytokinesis, cell growth, and cellular development. Our plan is to test our central hypothesis, and thus accomplish our overall objective for this project, by pursuing the following three specific aims: 1) Define the DnaA transcriptional regulon by analyzing the global chromosome profile of promoters bound by DnaA using chromatin immunoprecipitation assays followed by deep sequencing; 2) Identify regulators that modulate DnaA's activity at the origin of replication by cross-linking and isolating the chromosomal ori-proteins complex using a DNA-sampling technique; 3) Identify factors that directly interact with DnaA by isolating DnaA-containing protein complexes within the cell. Successful completion of the proposed research is expected to vertically advance and expand our knowledge of and ability to assemble the regulatory circuitry that controls Hp cell cycle. Furthermore, findings from our work will broaden our understanding of how the highly conserved replication initiators coordinate DNA synthesis with the progression of the cell cycle. Our proposed research is innovative, in our opinion, because it represents a substantive departure from the status quo by targeting Hp-specific cell cycle regulators as targets for new antibiotics.
项目总结/文摘

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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Paola E Mera其他文献

Chromosome dynamics in bacteria: triggering replication at opposite location and segregation in opposite direction
细菌中的染色体动力学:触发相反位置的复制和相反方向的分离
  • DOI:
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Ady B. Meléndez;Inoka P. Menikpurage;Paola E Mera
  • 通讯作者:
    Paola E Mera
The B12 receptor BtuB alters the membrane integrity of Caulobacter crescentus.
B12 受体 BtuB 改变新月柄杆菌的膜完整性。
  • DOI:
    10.1099/mic.0.000753
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    1.5
  • 作者:
    Inoka P. Menikpurage;D. Barraza;Ady B. Meléndez;Sierra Strebe;Paola E Mera
  • 通讯作者:
    Paola E Mera
Discovering and Applying the Urban Rules of Life to Design Sustainable and Healthy Cities.
发现并应用城市生活规则来设计可持续和健康的城市。
  • DOI:
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    2.6
  • 作者:
    T. A. Langen;C. Cannon;D. Blackburn;E. Morgan;Paola E Mera
  • 通讯作者:
    Paola E Mera
Chromosome Dynamics in Bacteria: Triggering Replication at the Opposite Location and Segregation in the Opposite Direction
细菌中的染色体动力学:触发相反位置的复制和相反方向的分离
  • DOI:
    10.1128/mbio.01002-19
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    6.4
  • 作者:
    Ady B. Meléndez;Inoka P. Menikpurage;Paola E Mera
  • 通讯作者:
    Paola E Mera

Paola E Mera的其他文献

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{{ truncateString('Paola E Mera', 18)}}的其他基金

Deciphering the molecular circuitry that controls cell cycle progression in bacteria
破译控制细菌细胞周期进程的分子电路
  • 批准号:
    10478051
  • 财政年份:
    2019
  • 资助金额:
    $ 14.8万
  • 项目类别:
Deciphering the molecular circuitry that controls cell cycle progression in bacteria
破译控制细菌细胞周期进程的分子电路
  • 批准号:
    10227369
  • 财政年份:
    2019
  • 资助金额:
    $ 14.8万
  • 项目类别:
Deciphering the molecular circuitry that controls cell cycle progression in bacteria
破译控制细菌细胞周期进程的分子电路
  • 批准号:
    10274049
  • 财政年份:
    2019
  • 资助金额:
    $ 14.8万
  • 项目类别:
Deciphering the molecular circuitry that controls cell cycle progression in bacteria
破译控制细菌细胞周期进程的分子电路
  • 批准号:
    10678741
  • 财政年份:
    2019
  • 资助金额:
    $ 14.8万
  • 项目类别:
Deciphering the molecular circuitry that controls cell cycle progression in bacteria
破译控制细菌细胞周期进程的分子电路
  • 批准号:
    10249364
  • 财政年份:
    2019
  • 资助金额:
    $ 14.8万
  • 项目类别:
Deciphering the molecular circuitry that controls cell cycle progression in bacteria
破译控制细菌细胞周期进程的分子电路
  • 批准号:
    10468560
  • 财政年份:
    2019
  • 资助金额:
    $ 14.8万
  • 项目类别:
Deciphering the molecular circuitry that controls cell cycle progression in bacteria
破译控制细菌细胞周期进程的分子电路
  • 批准号:
    10700095
  • 财政年份:
    2019
  • 资助金额:
    $ 14.8万
  • 项目类别:
Deciphering the molecular circuitry that controls cell cycle progression in bacteria
破译控制细菌细胞周期进程的分子电路
  • 批准号:
    9797583
  • 财政年份:
    2019
  • 资助金额:
    $ 14.8万
  • 项目类别:
The Spatial and Temporal Integration of Chromosome Segregation and Cytokinesis
染色体分离和细胞分裂的时空整合
  • 批准号:
    8125755
  • 财政年份:
    2011
  • 资助金额:
    $ 14.8万
  • 项目类别:
The Spatial and Temporal Integration of Chromosome Segregation and Cytokinesis
染色体分离和细胞分裂的时空整合
  • 批准号:
    8307562
  • 财政年份:
    2011
  • 资助金额:
    $ 14.8万
  • 项目类别:

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  • 资助金额:
    $ 14.8万
  • 项目类别:
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