Roles for host cytoskeletal, cell adhesion and membrane trafficking proteins in b
宿主细胞骨架、细胞粘附和膜运输蛋白在 b 中的作用
基本信息
- 批准号:8623547
- 负责人:
- 金额:$ 19.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-04-02 至 2016-03-31
- 项目状态:已结题
- 来源:
- 关键词:ActinsBacteriaCell AdhesionCell Adhesion MoleculesCell CommunicationCell membraneCell-Cell AdhesionCellsCommunicationConfocal MicroscopyCytoskeletonCytosolDiagnosisEndocytosisFeverGene SilencingImageImmune responseIndividualInfectionIntegration Host FactorsInvadedLeftLengthLifeLife Cycle StagesListeriaListeria monocytogenesListeriosisMembraneMembrane Protein TrafficMolecularNaturePathway interactionsPhagocytosisPlayProcessProteinsRNA InterferenceRickettsiaRoleSpottingsStagingTestingTimeTyphusVacuoleVirulenceWorkcell motilitycellular imagingcomparativehuman diseasenovel strategiespathogenprotein functionpublic health relevanceresearch study
项目摘要
DESCRIPTION (provided by applicant): Many bacterial athogens, including Listeria species and the spotted fever group (SFG) of Rickettsia species, invade host cells, escape from the invasion vacuole, and then grow in the cytosol, where they mobilize the host actin cytoskeleton to power intracellular motility and cell-to-cell spread. The ability of these bacteria to spread between cells without leaving the confines of the cell enables evasion of the humoral immune response, and is a key contributor to their virulence in spotted fever illness (R. rickettsii and R parkeri in the U.S.) and listeriosis (L. monocytogenes). Despite the importance of cell-to-cell spread in infection and virulence, this process is the most poorly understood stage in the intracellular life cycle of these pathogens. Cell-to-cell spread of Listeria and SFG Rickettsia occurs in steps that include collision with the donor cell membrane, formation of a protrusion, internalization of the protrusion into a vacuole by a recipient cell, and vacuole escape. However, we do not know which cellular pathways in the host are exploited by these pathogens at each step in this process. In the exploratory experiments proposed here, we will test the overall hypothesis that the steps of Listeria and Rickettsia spread require both overlapping and distinct sets of host proteins, including those important for cortical cytoskeletal function, cell adhesion,
phagocytosis and endocytosis. In particular, we will answer two questions. Which host proteins are functionally important for Rickettsia or Listeria spread, and is their role general or pathogen
specific? Moreover, at which stage of spread does each host protein act, and are they required in the donor or recipient cell? In Aim 1, we will carry out parallel RNAi screens, targeting 180 host factors important for cortical cytoskeleton function, cell-cell adhesion, phagocytosis and endocytosis, and evaluate the impact of gene silencing on both Rickettsia and Listeria spread. This comparative approach will reveal proteins and pathways that are generally important for pathogen spread, as well as those that are specifically important for each pathogen. In Aim 2, we will use a combination of RNAi and live cell imaging to test the specific hypotheses that cortical cytoskeleton and cell-cell adhesion proteins act in protrusion formation in the donor cell
and engulfment into the recipient cell, whereas phagocytosis and endocytosis proteins act in protrusion engulfment. Additionally, we will examine how each factor functions by determining its localization during spread and testing whether its activity is required in the donor or recipiet cell. Through these exploratory experiments, we will develop a framework for understanding crucial mechanisms of pathogen cell- to-cell spread that will set the stage for a more mechanistic understanding of this process. These studies may reveal new mechanisms of host-pathogen interactions, new approaches for diagnosing and treating infections, and new principles of cell-cell interaction and communication in uninfected cells.
描述(由申请人提供):许多细菌病原体,包括李斯特菌属和立克次氏体属的斑点热群(SFG),侵入宿主细胞,从侵入空泡中逃逸,然后在胞质溶胶中生长,在胞质溶胶中,它们动员宿主肌动蛋白细胞骨架,为细胞内运动和细胞间扩散提供动力。这些细菌在细胞之间传播而不离开细胞范围的能力使得能够逃避体液免疫应答,并且是它们在斑点热疾病中的毒力的关键因素(R.美国的立克次氏体和帕克氏体)和黑胫病(L.单核细胞增多症)。尽管细胞间传播在感染和毒力中的重要性,但这一过程是这些病原体细胞内生命周期中最不了解的阶段。李斯特菌和SFG立克次氏体的细胞间传播发生在包括与供体细胞膜碰撞、形成突起、突起被受体细胞内化到液泡中以及液泡逃逸的步骤中。然而,我们不知道在这个过程的每一步,这些病原体都利用了宿主中的哪些细胞途径。在这里提出的探索性实验中,我们将测试总体假设,即李斯特菌和立克次氏体传播的步骤需要重叠和不同的宿主蛋白质组,包括对皮质细胞骨架功能,细胞粘附,
吞噬作用和内吞作用。我们将特别回答两个问题。哪些宿主蛋白对立克次体或李斯特菌的传播具有重要的功能,它们的作用是一般性的还是病原性的
具体的?此外,每种宿主蛋白质在扩散的哪个阶段起作用,供体细胞或受体细胞是否需要它们?在目标1中,我们将进行平行RNAi筛选,靶向180个对皮质细胞骨架功能、细胞-细胞粘附、吞噬作用和内吞作用重要的宿主因子,并评估基因沉默对立克次体和李斯特菌传播的影响。这种比较方法将揭示通常对病原体传播重要的蛋白质和途径,以及对每种病原体特别重要的蛋白质和途径。在目标2中,我们将使用RNAi和活细胞成像的组合来测试皮质细胞骨架和细胞-细胞粘附蛋白在供体细胞中突起形成中起作用的特定假设
吞噬进入受体细胞,而吞噬作用和内吞作用蛋白在突起吞噬中起作用。此外,我们将通过确定其在扩散过程中的定位和测试其活性是否需要在供体或受体细胞中来检查每个因子的功能。通过这些探索性实验,我们将开发一个框架来理解病原体细胞到细胞传播的关键机制,这将为更机械地理解这一过程奠定基础。这些研究可能揭示宿主-病原体相互作用的新机制,诊断和治疗感染的新方法,以及未感染细胞中细胞-细胞相互作用和通信的新原理。
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 }}
Matthew D Welch其他文献
Matthew D Welch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('Matthew D Welch', 18)}}的其他基金
Exploring the role of type I interferon in Rickettsia pathogenesis
探讨I型干扰素在立克次体发病机制中的作用
- 批准号:
9888303 - 财政年份:2019
- 资助金额:
$ 19.56万 - 项目类别:
Exploring the role of type I interferon in Rickettsia pathogenesis
探讨I型干扰素在立克次体发病机制中的作用
- 批准号:
9764949 - 财政年份:2019
- 资助金额:
$ 19.56万 - 项目类别:
Microbial mobilization of the actin cytoskeleton
肌动蛋白细胞骨架的微生物动员
- 批准号:
9912779 - 财政年份:2018
- 资助金额:
$ 19.56万 - 项目类别:
Microbial mobilization of the actin cytoskeleton
肌动蛋白细胞骨架的微生物动员
- 批准号:
10623626 - 财政年份:2018
- 资助金额:
$ 19.56万 - 项目类别:
Microbial mobilization of the actin cytoskeleton
肌动蛋白细胞骨架的微生物动员
- 批准号:
10395934 - 财政年份:2018
- 资助金额:
$ 19.56万 - 项目类别:
Mechanisms of Rickettsia invasion, intracellular survival, and actin-based motility
立克次体侵袭、细胞内存活和基于肌动蛋白的运动的机制
- 批准号:
10461986 - 财政年份:2014
- 资助金额:
$ 19.56万 - 项目类别:
Roles for host cytoskeletal, cell adhesion and membrane trafficking proteins in b
宿主细胞骨架、细胞粘附和膜运输蛋白在 b 中的作用
- 批准号:
8830430 - 财政年份:2014
- 资助金额:
$ 19.56万 - 项目类别:
Mechanisms of Rickettsia invasion, intracellular survival, and actin-based motility
立克次体侵袭、细胞内存活和基于肌动蛋白的运动的机制
- 批准号:
9615323 - 财政年份:2014
- 资助金额:
$ 19.56万 - 项目类别:
Mechanisms of Rickettsia invasion, intracellular survival, and actin-based motility
立克次体侵袭、细胞内存活和基于肌动蛋白的运动的机制
- 批准号:
10238082 - 财政年份:2014
- 资助金额:
$ 19.56万 - 项目类别:
Rickettsia mobilization of the cytoskeleton during invasion, motility, and spread
立克次体在入侵、运动和扩散过程中动员细胞骨架
- 批准号:
8761830 - 财政年份:2014
- 资助金额:
$ 19.56万 - 项目类别:
相似国自然基金
Segmented Filamentous Bacteria激活宿主免疫系统抑制其拮抗菌 Enterobacteriaceae维持菌群平衡及其机制研究
- 批准号:81971557
- 批准年份:2019
- 资助金额:65.0 万元
- 项目类别:面上项目
电缆细菌(Cable bacteria)对水体沉积物有机污染的响应与调控机制
- 批准号:51678163
- 批准年份:2016
- 资助金额:64.0 万元
- 项目类别:面上项目
相似海外基金
Did light dictate ancient diversification of phylogeny and cell structure in the domain bacteria?
光是否决定了细菌领域的古代系统发育和细胞结构的多样化?
- 批准号:
24H00582 - 财政年份:2024
- 资助金额:
$ 19.56万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Cell Wall Formation in Rod Shaped Bacteria
杆状细菌细胞壁的形成
- 批准号:
BB/Y003187/1 - 财政年份:2024
- 资助金额:
$ 19.56万 - 项目类别:
Research Grant
DNA replication dynamics in living bacteria
活细菌中的 DNA 复制动态
- 批准号:
23K25843 - 财政年份:2024
- 资助金额:
$ 19.56万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Conference: Symposium on the Immune System of Bacteria
会议:细菌免疫系统研讨会
- 批准号:
2349218 - 财政年份:2024
- 资助金额:
$ 19.56万 - 项目类别:
Standard Grant
DYNBIOTICS - Understanding the dynamics of antibiotics transport in individual bacteria
DYNBIOTICS - 了解抗生素在单个细菌中转运的动态
- 批准号:
EP/Y023528/1 - 财政年份:2024
- 资助金额:
$ 19.56万 - 项目类别:
Research Grant
NPBactID - Differential binding of peptoid functionalized nanoparticles to bacteria for identifying specific strains
NPBactID - 类肽功能化纳米粒子与细菌的差异结合,用于识别特定菌株
- 批准号:
EP/Y029542/1 - 财政年份:2024
- 资助金额:
$ 19.56万 - 项目类别:
Fellowship
Assembly of the matrix that supports bacteria living in biofilms
支持生活在生物膜中的细菌的基质的组装
- 批准号:
2468773 - 财政年份:2024
- 资助金额:
$ 19.56万 - 项目类别:
Studentship
Manipulating two-component systems to activate cryptic antibiotic pathways in filamentous actinomycete bacteria
操纵双组分系统激活丝状放线菌中的神秘抗生素途径
- 批准号:
BB/Y005724/1 - 财政年份:2024
- 资助金额:
$ 19.56万 - 项目类别:
Research Grant
Engineering Streptomyces bacteria for the sustainable manufacture of antibiotics
工程化链霉菌用于抗生素的可持续生产
- 批准号:
BB/Y007611/1 - 财政年份:2024
- 资助金额:
$ 19.56万 - 项目类别:
Research Grant
CAREER: Interfacial behavior of motile bacteria at structured liquid crystal interfaces
职业:运动细菌在结构化液晶界面的界面行为
- 批准号:
2338880 - 财政年份:2024
- 资助金额:
$ 19.56万 - 项目类别:
Continuing Grant