ASSEMBLY OF THE DIVISION SEPTUM IN ESCHERICHIA COLI

大肠杆菌中隔膜的组装

基本信息

  • 批准号:
    6386604
  • 负责人:
  • 金额:
    $ 19.35万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1999
  • 资助国家:
    美国
  • 起止时间:
    1999-08-01 至 2004-07-31
  • 项目状态:
    已结题

项目摘要

The long-term focus of our work is cell division in bacteria. In particular, we are interested in how the division septum is formed, and how its formation is coordinated with other events in the cell- cycle such as chromosome segregation. An ancillary objective is to understand how proteins are localized to specific subcellular sites. This interest stems from the observation that many proteins involved in septum assembly are localized to the division site. Cell division and protein localization are fundamental cellular processes of importance to all organisms, including humans, and underlie diseases such as cancer, but are often difficult to study due to technical limitations. The wealth of genetic tools available in Escherichia coli makes this an ideal model organism for studies of basic cellular processes. Septum assembly in E. coli requires at least nine essential proteins, all of which localize to the division site. Our hypothesis is that these proteins form of complex that contains all of the activities need for septum assembly, and that interactions among these proteins are important for their recruitment to the division site and for regulating their activities. Thus, we want to know more about the detailed function of these proteins, to identify interactions among these proteins, and to know whether the set is complete. To approach these issues we will characterize FtsI, a membrane protein with an enzymatic activity (transpeptidase) related to peptidoglycan synthesis. Specifically, we will (i) use a combination of genetics and fluorescence microscopy to identify sequences in FtsI that target this protein to the division site; (ii) use biochemical and genetic approaches to look for proteins that interact directly with FtsI; and (iii) use fluorescence microscopy to determine the subcellular location of three transglycosylases postulated to be involved in synthesis of septal peptidoglycan and to interact with FtsI. A better understanding of cell division in a simple bacterial system might shed light on these processes in other organisms, including humans. In addition, a better understanding of these processes might lead to more knowledge-based approaches to developing new antibiotics. In this regard, it is worth noting that four of the proteins to be studied here (FtsI and the three transglycosylases) are primary targets of beta-lactam antibiotics.
我们工作的长期重点是细菌的细胞分裂。特别是,我们感兴趣的是分裂隔膜是如何形成的,以及它的形成是如何与细胞周期中的其他事件如染色体分离相协调的。一个辅助目标是了解蛋白质是如何定位到特定的亚细胞位点。这种兴趣源于观察到,许多蛋白质参与隔膜组装定位于分裂网站。细胞分裂和蛋白质定位是对包括人类在内的所有生物体都很重要的基本细胞过程,并且是癌症等疾病的基础,但由于技术限制,通常难以研究。大肠杆菌中丰富的遗传工具使其成为研究基本细胞过程的理想模式生物。E.大肠杆菌需要至少九种必需蛋白质,所有这些蛋白质都定位于分裂位点。我们的假设是,这些蛋白质形成的复合物,包含所有的活动需要隔膜组装,这些蛋白质之间的相互作用是重要的,他们的招聘分裂网站和调节他们的活动。因此,我们想知道更多关于这些蛋白质的详细功能,以确定这些蛋白质之间的相互作用,并知道该集合是否完整。为了解决这些问题,我们将表征FtsI,一种具有与肽聚糖合成相关的酶活性(转肽酶)的膜蛋白。 具体来说,我们将(i)使用遗传学和荧光显微镜的组合来识别FtsI中将该蛋白质靶向分裂位点的序列;(ii)使用生物化学和遗传学方法来寻找与FtsI直接相互作用的蛋白质;和(iii)使用荧光显微镜确定假定参与隔肽聚糖合成并与FtsI相互作用的三种转糖基酶的亚细胞位置。更好地了解简单细菌系统中的细胞分裂可能会为包括人类在内的其他生物体中的这些过程提供线索。 此外,更好地了解这些过程可能会导致更多基于知识的方法来开发新的抗生素。在这方面,值得注意的是,这里要研究的四种蛋白质(FtsI和三种转糖基酶)是β-内酰胺抗生素的主要靶标。

项目成果

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DAVID S WEISS其他文献

DAVID S WEISS的其他文献

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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:
    $ 19.35万
  • 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:
    $ 19.35万
  • 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:
    10518406
  • 财政年份:
    2021
  • 资助金额:
    $ 19.35万
  • 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:
    $ 19.35万
  • 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:
    $ 19.35万
  • 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:
    $ 19.35万
  • 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:
    $ 19.35万
  • 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:
    $ 19.35万
  • 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:
    $ 19.35万
  • 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:
    $ 19.35万
  • 项目类别:

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职业:阐明聚糖纳米​​材料与细菌蛋白质、毒素和细胞的协同纳米级和碳水化合物相互作用
  • 批准号:
    2142579
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    2022
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Development of machine learning methods for automated design of new biological functions in bacterial proteins.
开发机器学习方法,用于自动设计细菌蛋白质的新生物功能。
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    2600923
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    2021
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    526817-2018
  • 财政年份:
    2018
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细菌蛋白作为配方成分。
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生产难以表达的必需细菌蛋白
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  • 财政年份:
    2016
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    $ 19.35万
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分泌细菌蛋白的磷酸化和乙酰化:新的调控
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奈瑟氏球菌的蛋白质 O-糖基化途径:细菌蛋白质 O-糖基化的模型系统,具有生物技术的潜在用途
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  • 财政年份:
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利用细菌蛋白阐明基质锚定分子机制的临床前研究
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    23590516
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细菌蛋白 YjeE、YeaZ 和 YgjD 的表征以及作为潜在新型抗菌靶点的评估
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