Mechanisms of ESX-1-dependent Gene Expression in Pathogenic Mycobacteria
病原分枝杆菌中 ESX-1 依赖性基因表达的机制
基本信息
- 批准号:10078256
- 负责人:
- 金额:$ 19.31万
- 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:2020-01-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffinityBacteriaBiochemicalBiologicalCell membraneCytolysisCytoplasmDNADataDiagnosisELF3 geneEpidemicFishesGene ExpressionGene Expression RegulationGenesGeneticGenetic ScreeningGenetic TranscriptionGenus MycobacteriumGoalsHumanInfectionIntegral Membrane ProteinKnowledgeLaboratoriesLeadLeftLinkMediatingMembraneMetabolismMissionModelingMolecularMycobacterium marinumMycobacterium tuberculosisOutcomePathogenesisPathogenicityPathway interactionsPhagosomesPhasePreventionProteinsPublic HealthPublishingRegulationResearchRoleSignal PathwaySignal TransductionSignal Transduction PathwaySolidSystemTestingTuberculosisUnited States National Institutes of HealthVirulence FactorsWorkgene discoverygenetic testinginnovationinsightmacrophagemycobacterialpathogenpreventpromoterresponsetherapeutic developmenttranscription factortuberculosis treatmentvaccine development
项目摘要
PROJECT SUMMARY:
The applicant’s laboratory discovered that the assembly of the ESX-1 translocon in the cytoplasmic membrane
regulates gene expression. The long-term goal of the applicant is to understand the biological significance of
ESX-1-dependent changes in gene expression. The applicant proposes that the assembly of the ESX-1 trans-
locon elicits gene expression pathways that couple phagosomal lysis and adaptation to cytoplasmic exposure.
The overall objective of this proposal is to explore how the ESX-1 translocon regulates gene expression, which
will contribute to addressing the applicant’s long-term goal. The central hypothesis is that there is an uncharac-
terized transcription response network connecting the ESX-1 translocon to widespread changes in gene expres-
sion, potentially linking phagosomal lysis and cytoplasmic adaptation. The rationale is that the successful com-
pletion of the proposed work will provide insight into the fundamental mechanisms linking lysis of the phagosomal
membrane by ESX-1 with changes in gene expression. The central hypothesis will be tested by following these
specific aims: 1) Identify the transcription factor network that regulates ESX-1-dependent gene expression. 2)
Define the genes required for ESX-1-dependent signal transduction. Under the first aim, the applicant proposes
to use genetic, molecular and biochemical approaches to identify transcription factors and genes in the tran-
scriptional network that responds to the ESX-1 translocon. Under the second aim, the applicant proposes to use
genetic and molecular approaches to identify and characterize genes and signaling pathways that connect the
translocon in the cytoplasmic membrane to changes in gene expression. The expected outcome following the
successful completion of the proposed aims will be to define factors and pathways required for ESX-1-dependent
changes in mycobacterial gene expression. This contribution will be significant because it will provide fundamen-
tal insight into the regulation of bacterial factors that promote interaction with the host during the initial phases of
infection, positively impacting our ability to prevent diagnose and treat TB. The proposed research is technically
and conceptually innovative. Previous work on ESX-1 has focused on the mechanisms of secretion by and the
effects of the ESX-1 system on the host. The proposed work focuses on the role of the ESX-1 system in regu-
lating transcriptional response networks, which has not been previously considered. To the applicant’s
knowledge, considering the assembly of the ESX-1 translocon as a signal that elicits changes in gene expression
is a new idea. Finally, the combined multi-pronged approach to identify the mechanisms connecting the ESX-1
translocon to gene expression is innovative. Defining the molecular mechanisms underlying the control of gene
expression by the ESX- translocon will advance the field by providing new mechanisms regulating mycobacterial
gene expression.
项目概要:
申请人的实验室发现,ESX-1易位子在细胞质膜中的组装
调节基因表达。申请人的长期目标是了解
基因表达中的ESX-1依赖性变化。申请人建议ESX-1反式-
locon eligible基因表达途径,将吞噬体溶解和适应与细胞质暴露相结合。
本研究的总体目标是探索ESX-1易位子如何调节基因表达,
有助于实现申请人的长期目标。中心假设是存在一个uncharac-
将ESX-1转位子与基因表达的广泛变化联系起来的标准化转录反应网络,
锡永将吞噬体溶解和细胞质适应联系起来。理由是,成功的COM-
所提出的工作的一部分将提供深入了解的基本机制,连接裂解的吞噬体
ESX-1对细胞膜的影响及基因表达的变化。中心假设将通过以下方式进行检验:
具体目标:1)鉴定调节ESX-1依赖性基因表达的转录因子网络。(二)
定义ESX-1依赖性信号转导所需的基因。在第一个目标下,申请人提出
利用遗传学、分子生物学和生物化学方法来鉴定转录因子和基因,
响应ESX-1 translocon的脚本网络。根据第二个目标,申请人建议使用
基因和分子方法来识别和表征基因和信号通路,
细胞质膜中的易位子与基因表达的变化有关。预期成果
成功完成拟议目标的关键是确定ESX-1依赖型
分枝杆菌基因表达的变化。这一贡献将是重要的,因为它将提供基础-
深入了解细菌因子的调节,促进与宿主在初始阶段的相互作用,
感染,积极影响我们预防诊断和治疗结核病的能力。这项研究在技术上
在概念上创新。以前对ESX-1的研究主要集中在细胞分泌的机制上,
ESX-1系统对主机的影响。建议的工作重点是ESX-1系统在regu中的作用,
转录反应网络,这是以前没有考虑过的。申请人的
知识,认为ESX-1易位子的组装是引起基因表达变化的信号
是一个新的想法。最后,结合多管齐下的方法来确定连接ESX-1的机制
转座基因表达是创新的。定义基因调控的分子机制
通过ESX-易位子的表达将通过提供调节分枝杆菌的新机制来推进该领域
基因表达。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Patricia A Champion其他文献
Patricia A Champion的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Patricia A Champion', 18)}}的其他基金
Molecular Genetics of Bacteria and Phages Conference (The Phage Meeting)
细菌和噬菌体分子遗传学会议(噬菌体会议)
- 批准号:
10752758 - 财政年份:2023
- 资助金额:
$ 19.31万 - 项目类别:
Investigating the molecular requirements for ESX-1-lytic activity in pathogenic mycobacteria
研究致病性分枝杆菌 ESX-1 裂解活性的分子需求
- 批准号:
10374860 - 财政年份:2021
- 资助金额:
$ 19.31万 - 项目类别:
The requirement for PDIM in mycobacterial protein secretion
分枝杆菌蛋白分泌对 PDIM 的要求
- 批准号:
10183155 - 财政年份:2020
- 资助金额:
$ 19.31万 - 项目类别:
Role of N-alpha acetylation in mycobacterial secretion and virulence
N-α 乙酰化在分枝杆菌分泌和毒力中的作用
- 批准号:
8830915 - 财政年份:2013
- 资助金额:
$ 19.31万 - 项目类别:
Mechanisms and Consequences of Mycobacterial N-terminal Protein Acetylation
分枝杆菌 N 末端蛋白质乙酰化的机制和后果
- 批准号:
10264092 - 财政年份:2013
- 资助金额:
$ 19.31万 - 项目类别:
Mechanisms and Consequences of Mycobacterial N-terminal Protein Acetylation
分枝杆菌 N 末端蛋白质乙酰化的机制和后果
- 批准号:
10680597 - 财政年份:2013
- 资助金额:
$ 19.31万 - 项目类别:
Mechanisms and Consequences of Mycobacterial N-terminal Protein Acetylation
分枝杆菌 N 末端蛋白质乙酰化的机制和后果
- 批准号:
10462800 - 财政年份:2013
- 资助金额:
$ 19.31万 - 项目类别:
Role of N-alpha acetylation in mycobacterial secretion and virulence
N-α 乙酰化在分枝杆菌分泌和毒力中的作用
- 批准号:
8558419 - 财政年份:2013
- 资助金额:
$ 19.31万 - 项目类别:
Role of N-alpha acetylation in mycobacterial secretion and virulence
N-α 乙酰化在分枝杆菌分泌和毒力中的作用
- 批准号:
8660632 - 财政年份:2013
- 资助金额:
$ 19.31万 - 项目类别:
Comprehensive Identification of the Genetic Requirements for ESX-1 Secretion
全面鉴定 ESX-1 分泌的遗传要求
- 批准号:
8268348 - 财政年份:2011
- 资助金额:
$ 19.31万 - 项目类别:
相似海外基金
Construction of affinity sensors using high-speed oscillation of nanomaterials
利用纳米材料高速振荡构建亲和传感器
- 批准号:
23H01982 - 财政年份:2023
- 资助金额:
$ 19.31万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Affinity evaluation for development of polymer nanocomposites with high thermal conductivity and interfacial molecular design
高导热率聚合物纳米复合材料开发和界面分子设计的亲和力评估
- 批准号:
23KJ0116 - 财政年份:2023
- 资助金额:
$ 19.31万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Development of High-Affinity and Selective Ligands as a Pharmacological Tool for the Dopamine D4 Receptor (D4R) Subtype Variants
开发高亲和力和选择性配体作为多巴胺 D4 受体 (D4R) 亚型变体的药理学工具
- 批准号:
10682794 - 财政年份:2023
- 资助金额:
$ 19.31万 - 项目类别:
Platform for the High Throughput Generation and Validation of Affinity Reagents
用于高通量生成和亲和试剂验证的平台
- 批准号:
10598276 - 财政年份:2023
- 资助金额:
$ 19.31万 - 项目类别:
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
- 批准号:
2233343 - 财政年份:2023
- 资助金额:
$ 19.31万 - 项目类别:
Standard Grant
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
- 批准号:
2233342 - 财政年份:2023
- 资助金额:
$ 19.31万 - 项目类别:
Standard Grant
Molecular mechanisms underlying high-affinity and isotype switched antibody responses
高亲和力和同种型转换抗体反应的分子机制
- 批准号:
479363 - 财政年份:2023
- 资助金额:
$ 19.31万 - 项目类别:
Operating Grants
Deconstructed T cell antigen recognition: Separation of affinity from bond lifetime
解构 T 细胞抗原识别:亲和力与键寿命的分离
- 批准号:
10681989 - 财政年份:2023
- 资助金额:
$ 19.31万 - 项目类别:
CAREER: Engineered Affinity-Based Biomaterials for Harnessing the Stem Cell Secretome
职业:基于亲和力的工程生物材料用于利用干细胞分泌组
- 批准号:
2237240 - 财政年份:2023
- 资助金额:
$ 19.31万 - 项目类别:
Continuing Grant
ADVANCE Partnership: Leveraging Intersectionality and Engineering Affinity groups in Industrial Engineering and Operations Research (LINEAGE)
ADVANCE 合作伙伴关系:利用工业工程和运筹学 (LINEAGE) 领域的交叉性和工程亲和力团体
- 批准号:
2305592 - 财政年份:2023
- 资助金额:
$ 19.31万 - 项目类别:
Continuing Grant