Project 4. Defining cell division pathways in Mtb.
Project 4. Defining cell division pathways in Mtb.
批准号:
10426182
负责人:
SABINE EHRT
金额:
$70.46万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
未结题
起止时间:
2020-06-12 至 2025-05-31
关键词:
Animal ModelBacillus subtilisBacteriaBiochemicalCell CycleCell Division ProcessCell WallCell divisionCell modelCell physiologyCellular Metabolic ProcessCellular StructuresCollaborationsComplexCore FacilityCuesCytokinesisDNA biosynthesisDataDiseaseEnzymesEscherichia coliEventGenesGeneticGenetic TranscriptionGenus MycobacteriumGoalsGuanosineInfectionLinkMediator of activation proteinMetabolicMetabolic PathwayMetabolismMethodsMorphogenesisMycobacterium tuberculosisNucleosidesPathway AnalysisPathway interactionsPhosphorylationProcessProtein KinaseRegulationRoleStressTuberculosisWorkantimicrobialbasecell assemblycell growthgene productmetabolomicsmycobacterialperiplasmprogramsprotein complexprotein protein interactionquantitative imagingsegregation
中文摘要
项目4,摘要
英文摘要
Project 4, Abstract
Like all bacteria, Mycobacterium tuberculosis (Mtb) must coordinate major cellular processes, such as DNA
replication, with the synthesis and segregation of structural components in order to grow and divide. While the
processes governing cell division are reasonably well-described in model organisms, the mechanisms used by
mycobacteria are clearly different and less well understood. Defining the mechanisms governing the essential
process of cell division in Mtb will reveal new antimicrobial targets and provide the basis to understand how this
process is regulated during the slow-growing states that contribute to bacterial persistence during infection. This
project supports the program’s overall goal to understand pathways important to Mtb’s adaptation to
disease-relevant stress. It will synergize with other projects and leverage each of the cores.
Coordinating the cytokinesis with the cell cycle and the distribution of cellular material must be both temporally
and spatially regulated. Work in the project labs has shown that this coordination requires at least three distinct
regulatory paradigms. (1) The ordered assembly of the cell division complex, or “divisome” requires spatial and
temporal cues that may be provided by Ser/Thr protein kinases (STPK). (2) Extracytoplasmic enzymes
responsible for cell wall metabolism represent a distinct regulatory challenge, and are often controlled by protein-
protein interactions in the periplasmic space. (3) The coordination of processes necessary for cell division are
not restricted to the septum; fundamental metabolic changes are also likely necessary to provide the precursors
required for this major cellular event.
The goal of this project is to understand the regulatory paradigms that control mycobacterial cell division.
Specifically, the project will:
Aim 1. Characterize the role of protein phosphorylation in divisome dynamics. Synchronized Mtb cultures,
quantitative imaging, and biochemical approaches will be used to mechanistically characterize the role of
phosphorylation in the temporal and spatial regulation of divisome function.
Aim 2. Define and characterize extracytoplasmic complexes necessary for cell division. A combination of
genetic and physical approaches will be used to find interactions that are important for regulating enzymatic
activity and localization during cell division.
Aim 3. Characterize the links between cell division and metabolism. A combination of metabolomics and
genetics will be used to investigate the primary metabolic pathways necessary for cell division.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
M. tuberculosis carbon metabolism during infection
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批准号:10716619
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项目类别:
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资助金额:$65.23万
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财政年份:2023
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负责人:SABINE EHRT
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依托单位:
Tri-Institutional TRAC Basic Science Core
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批准号:10430741
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项目类别:
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财政年份:2022
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依托单位:
Tri-Institutional TRAC Basic Science Core
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批准号:10675748
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项目类别:
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财政年份:2022
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负责人:SABINE EHRT
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依托单位:
Turning Mycobacterium tuberculosis appetite for fatty acids against itself
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批准号:10592602
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项目类别:
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财政年份:2022
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负责人:SABINE EHRT
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依托单位:
Determinants of TB control, relapse and reinfection
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批准号:10268801
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项目类别:
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资助金额:$275.55万
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财政年份:2021
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负责人:SABINE EHRT
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依托单位:
Determinants of TB control, relapse and reinfection
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批准号:10621299
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项目类别:
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资助金额:$256.5万
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财政年份:2021
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负责人:SABINE EHRT
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依托单位:
Admin Core
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批准号:10268802
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项目类别:
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资助金额:$14.12万
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财政年份:2021
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负责人:SABINE EHRT
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依托单位:
Determinants of Paucibacillary Mtb Infection in Mice
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批准号:10430228
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项目类别:
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资助金额:$57.25万
-
财政年份:2021
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负责人:SABINE EHRT
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依托单位:
Determinants of TB control, relapse and reinfection
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批准号:10430221
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项目类别:
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资助金额:$258.33万
-
财政年份:2021
-
负责人:SABINE EHRT
-
依托单位:
Determinants of Paucibacillary Mtb Infection in Mice
-
批准号:10268807
-
项目类别:
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资助金额:$45.99万
-
财政年份:2021
-
负责人:SABINE EHRT
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依托单位:
Determinants of Paucibacillary Mtb Infection in Mice
-
批准号:10621309
-
项目类别:
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资助金额:$45.82万
-
财政年份:2021
-
负责人:SABINE EHRT
-
依托单位:
Admin Core
-
批准号:10430222
-
项目类别:
-
资助金额:$18.43万
-
财政年份:2021
-
负责人:SABINE EHRT
-
依托单位:
Microbiome in TB treatment response and disease resolution
-
批准号:10430225
-
项目类别:
-
资助金额:$49.94万
-
财政年份:2021
-
负责人:SABINE EHRT
-
依托单位:
Microbiome in TB treatment response and disease resolution
-
批准号:10268805
-
项目类别:
-
资助金额:$54.7万
-
财政年份:2021
-
负责人:SABINE EHRT
-
依托单位:
Admin Core
-
批准号:10621300
-
项目类别:
-
资助金额:$13.15万
-
财政年份:2021
-
负责人:SABINE EHRT
-
依托单位:
Microbiome in TB treatment response and disease resolution
-
批准号:10621304
-
项目类别:
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资助金额:$48.48万
-
财政年份:2021
-
负责人:SABINE EHRT
-
依托单位:
Project 1. Metabolic adaptations required for growth and virulence of Mtb at acidic pH.
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批准号:10426179
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项目类别:
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资助金额:$29.28万
-
财政年份:2020
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负责人:SABINE EHRT
-
依托单位:
Core D. Administration Core
-
批准号:10426175
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项目类别:
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资助金额:$6.34万
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财政年份:2020
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负责人:SABINE EHRT
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依托单位:
Project 1. Metabolic adaptations required for growth and virulence of Mtb at acidic pH.
-
批准号:10641874
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项目类别:
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资助金额:$28.77万
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财政年份:2020
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负责人:SABINE EHRT
-
依托单位:
Project 4. Defining cell division pathways in Mtb.
-
批准号:10641888
-
项目类别:
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资助金额:$66.87万
-
财政年份:2020
-
负责人:SABINE EHRT
-
依托单位:
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