Organization of Toxoplasma invasion and cell division by EF-hand proteins
EF-hand 蛋白组织弓形虫入侵和细胞分裂
基本信息
- 批准号:8661114
- 负责人:
- 金额:$ 7.83万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-05-14 至 2016-04-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAffinityAmino AcidsBindingBinding ProteinsCalcineurinCalmodulinCalmodulin-Binding ProteinsCell CycleCell Division ProcessCell divisionCellsCentrosomeComplementComplexCongenital AbnormalityContractsCre-LoxPCytoskeletonDNA RepairDataDaughterDiseaseDissectionEF Hand MotifsEF-Hand DomainEncephalitisEssential GenesEventFamilyFamily memberFutureGene FamilyGenesGenomeGoalsHelix-Loop-Helix MotifsImmune responseImmunocompromised HostInfectionIonophoresIonsKnock-outLeadLifeLife Cycle StagesLiftingLightLyticLytic PhaseMammalian CellMediatingMitosisNamesNonmuscle Myosin Type IIAOrganellesOrganismOrthologous GeneParasitesPathogenesisPathologyPatternPlayProcessProtein DynamicsProtein FamilyProteinsResearch PersonnelRoleSignal PathwaySignal Transduction PathwayStructureTimeTissuesToxoplasmaToxoplasma gondiiTranslatingTrimethoprim-SulfamethoxazoleWorkcalcineurin phosphatasecalcium-dependent protein kinasecell motilityextracellularfollow-upinsightmembermutantprotein functionpublic health relevanceresearch studysegregation
项目摘要
DESCRIPTION (provided by applicant): The apicomplexan parasite Toxoplasma gondii is the causative agent of life-threatening encephalitis in immunocompromised patients and in addition can cause a variety of birth defects if the infection is contracted congenitally. The pathology associated with disease originates in fast rounds of lytic intracellular replication cycles, causin extensive tissue damage. Since parasite replication only occurs within a cell from the mammalian host, the related processes of host cell invasion and egress mark essential steps in the pathogenesis. It has been firmly established that the signaling pathways underlying invasion and egress revolve around the cytoplasmic rise of Ca2+ concentration. Two small, Ca2+-binding proteins, calmodulin (CaM; 4 EF-hands) and the calcineurin phosphatase (the regulatory ¿-subunit has 4 EF hands), have been associated with activation of egress/invasion through pharmacological studies. Furthermore, a related group of small, 4-EF-hand containing proteins consisting of three centrins (Cen1-3) are critical components to the cell division machinery: Cen1 and Cen3 in centrosome duplication, required for mitosis and coordination of the unusual cell division process; Cen2 in contraction of the basal complex required for daughter parasite segregation. In essence, this family of EF-hand proteins plays pivotal roles in the defining steps of pathogenesis: invasion/egress and cell division. However this protein family has never been comprehensively studied, despite their critical roles in pathogenesis. To fill this void, the researchers identified a total of 16 such proteins in the genome, most of which have not been studied at all but likely execute additional functions in these processes. Preliminary sub-cellular
localization dynamics of these proteins throughout the lytic cycle support this hypothesis and permits putative assignment to roles in cell division or invasion/egress. It is proposed to complete these preliminary studies for the whole family followed by conditional gene knock-outs of the ten prioritized candidates. To illustrate the power of this approach, these experiments will
for the first time directly address whether CaM or calcineurin have a role in egress/invasion, for which only indirect pharmacological data is currently available. Furthermore, using the Cen2 and CaM as a pilot, the direct dissection of the role of Ca2+-binding in the family members with critical roles in invasion or cell division will be pioneered. It is anticipated that these studieswill lift the veil on the enigmatic role of Cen2 in Toxoplasma cell division and/or cytoskeleton structure. In conclusion, this study of a poorly studied gene family is expected to provide key insights into two key aspects in apicomplexan parasite pathogenesis.
描述(由申请人提供):弓形虫是免疫功能低下患者危及生命的脑炎病原体,此外,如果感染是先天性的,还可能导致多种出生缺陷。与疾病相关的病理起源于快速的细胞内裂解复制周期,引起广泛的组织损伤。由于寄生虫的复制只发生在哺乳动物宿主的一个细胞内,因此宿主细胞的入侵和退出的相关过程标志着其发病机制的重要步骤。它已经坚定地确立了信号通路的入侵和出口围绕细胞质Ca2+浓度的上升。两个小的Ca2+结合蛋白,钙调蛋白(CaM; 4个EF-hand)和钙调磷酸酶(调节亚基有4个EF-hand),通过药理学研究与出口/入侵的激活有关。此外,一组包含3个中心体(Cen1-3)的含有4-EF-hand的小蛋白质是细胞分裂机制的关键组成部分:中心体复制中的Cen1和Cen3是有丝分裂和不寻常的细胞分裂过程协调所必需的;Cen2在子寄生分离所需的基础复合体的收缩中起作用。从本质上讲,EF-hand蛋白家族在确定发病机制的步骤中起着关键作用:侵袭/输出和细胞分裂。然而,尽管该蛋白家族在发病机制中起着关键作用,但尚未对其进行全面研究。为了填补这一空白,研究人员在基因组中发现了16种这样的蛋白质,其中大多数根本没有被研究过,但可能在这些过程中执行额外的功能。初步的亚细胞
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 }}
Marc-Jan Gubbels其他文献
Marc-Jan Gubbels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('Marc-Jan Gubbels', 18)}}的其他基金
Defining the shared transcriptional network underlying Toxoplasma extracellular stress and stage transition
定义弓形虫细胞外应激和阶段转变背后的共享转录网络
- 批准号:
10682134 - 财政年份:2023
- 资助金额:
$ 7.83万 - 项目类别:
Mapping the protein landscape of the Toxoplasma basal complex
绘制弓形虫基础复合物的蛋白质图谱
- 批准号:
9387832 - 财政年份:2017
- 资助金额:
$ 7.83万 - 项目类别:
Proteomic mapping of differential secretion in Toxoplasma gondii
弓形虫差异分泌的蛋白质组图谱
- 批准号:
9228917 - 财政年份:2016
- 资助金额:
$ 7.83万 - 项目类别:
The Ca2+-sensing machinery operating on exocytosis in Toxoplasma
弓形虫胞吐作用中的 Ca2 感应机制
- 批准号:
9203658 - 财政年份:2016
- 资助金额:
$ 7.83万 - 项目类别:
The Ca2+-sensing machinery operating on exocytosis in Toxoplasma
弓形虫胞吐作用中的 Ca2 感应机制
- 批准号:
9927576 - 财政年份:2016
- 资助金额:
$ 7.83万 - 项目类别:
Dissecting the mechanism and regulation of Toxoplasma cytokinesis
剖析弓形虫胞质分裂的机制和调控
- 批准号:
9128297 - 财政年份:2015
- 资助金额:
$ 7.83万 - 项目类别:
The role of the DOC2.1 protein in Toxoplasma gondii Ca2+- dependent exocytosis
DOC2.1蛋白在弓形虫Ca2依赖性胞吐作用中的作用
- 批准号:
8716658 - 财政年份:2013
- 资助金额:
$ 7.83万 - 项目类别:
Organization of Toxoplasma invasion and cell division by EF-hand proteins
EF-hand 蛋白组织弓形虫入侵和细胞分裂
- 批准号:
8569583 - 财政年份:2013
- 资助金额:
$ 7.83万 - 项目类别:
相似海外基金
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 7.83万 - 项目类别:
Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 7.83万 - 项目类别:
Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 7.83万 - 项目类别:
Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 7.83万 - 项目类别:
Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 7.83万 - 项目类别:
Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 7.83万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 7.83万 - 项目类别:
Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
- 批准号:
2301846 - 财政年份:2023
- 资助金额:
$ 7.83万 - 项目类别:
Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 7.83万 - 项目类别:
Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
- 批准号:
23K16076 - 财政年份:2023
- 资助金额:
$ 7.83万 - 项目类别:
Grant-in-Aid for Early-Career Scientists