Functional investigation of a novel and essential subcellular compartment in Plasmodium falciparum transmission stage parasites

恶性疟原虫传播阶段寄生虫中新型重要亚细胞区室的功能研究

基本信息

  • 批准号:
    10584525
  • 负责人:
  • 金额:
    $ 75.31万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-03-04 至 2027-02-28
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Malaria is an important cause of illness and death worldwide, with most of these deaths resulting from Plasmodium falciparum infection. Successful completion of the P. falciparum life cycle and infection of a new human host requires transmission. During the asexual blood stage in human red blood cells, a small population of parasites differentiates into transmission forms known as gametocytes. These gametocytes can complete the sexual stage of the parasite life cycle following ingestion by a mosquito. Gametocyte maturation in human red blood cells occurs over 10-12 days and is associated with major changes in cellular morphology and rigidity. A newly discovered protein PfBLEB (for Baso-Lateral Expansion Boundary) is essential for mature gametocyte formation. In asexual parasites, PfBLEB is part of the basal complex, a ring-like multi-protein complex at the leading edge of the inner membrane complex. While PfBLEB is dispensable for both asexual replication and gametocyte commitment, it is essential for gametocyte development. PfBLEB-knockdown or knockout gametocytes arrest during maturation and are non- transmissible. Furthermore, the PfBLEB-deficient gametocytes have gross morphologic changes with defects in major cytoskeletal features of the maturing transmission-stage parasite, including the inner membrane complex and subpellicular microtubules. In gametocytes with normal PfBLEB expression, PfBLEB defines a new subcellular compartment within the parasite, demarcating the regions of the parasite plasma membrane that are devoid of the underlying inner membrane complex. The PfBLEB-compartment is essential for gametocyte development, but the function and protein constituents of this newly discovered subcellular compartment remain unknown. The goal of the current application is to define and genetically evaluate the protein components of the PfBLEB compartment and to understand the functional defects in PfBLEB-deficient gametocytes. The first aim will utilize proximity labeling and reverse genetics to explore the PfBLEB-containing compartment. The second aim will utilize multiple imaging and microfabrication techniques to gain a functional understanding of what processes are abnormal in PfBLEB-deficient gametocytes. Together, the proposed studies will add a new layer to our molecular understanding of gametocyte development in P. falciparum.
项目概要 疟疾是全世界疾病和死亡的重要原因,其中大部分死亡是由疟疾引起的 恶性疟原虫感染。成功完成恶性疟原虫的生命周期并感染 新的人类宿主需要传播。在人类红细胞的无性血液阶段,一个小的 寄生虫群体分化成称为配子体的传播形式。这些配子体 被蚊子摄入后可以完成寄生虫生命周期的有性阶段。配子体 人类红细胞的成熟过程需要 10-12 天,并且与 细胞形态和刚性。新发现的蛋白质 PfBLEB(用于基底外侧扩展边界) 对于成熟配子体的形成至关重要。在无性寄生虫中,PfBLEB 是基底复合体的一部分, 在内膜复合物前沿的环状多蛋白复合物。虽然 PfBLEB 是 对于无性复制和配子细胞定型来说都是可有可无的,但它对于配子细胞来说是必不可少的 发展。 PfBLEB 敲低或敲除配子细胞在成熟过程中停滞,并且是非 可传播的。此外,PfBLEB 缺陷的配子细胞具有明显的形态变化 成熟传播阶段寄生虫主要细胞骨架特征的缺陷,包括内部 膜复合体和膜下微管。 在具有正常 PfBLEB 表达的配子细胞中,PfBLEB 在配子细胞内定义了一个新的亚细胞区室。 寄生虫,划分寄生虫质膜的区域,这些区域没有底层的内部 膜复合物。 PfBLEB 区室对于配子体发育至关重要,但其功能 这个新发现的亚细胞区室的蛋白质成分仍然未知。的目标 目前的应用是定义和遗传评估 PfBLEB 隔室的蛋白质成分 并了解 PfBLEB 缺陷配子细胞的功能缺陷。第一个目标将利用邻近性 标记和反向遗传学来探索包含 PfBLEB 的隔室。第二个目标将利用 多种成像和微加工技术,以获得对流程的功能性理解 PfBLEB 缺陷的配子细胞异常。总之,拟议的研究将为我们的研究增添一个新的层面 恶性疟原虫配子体发育的分子理解。

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 }}

JEFFREY D DVORIN其他文献

JEFFREY D DVORIN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('JEFFREY D DVORIN', 18)}}的其他基金

Functional characterization of striated fiber assemblins in malaria parasites
疟疾寄生虫中横纹纤维组装体的功能特征
  • 批准号:
    10675782
  • 财政年份:
    2023
  • 资助金额:
    $ 75.31万
  • 项目类别:
Functional investigation of a novel and essential subcellular compartment in Plasmodium falciparum transmission stage parasites
恶性疟原虫传播阶段寄生虫中新型重要亚细胞区室的功能研究
  • 批准号:
    10458816
  • 财政年份:
    2022
  • 资助金额:
    $ 75.31万
  • 项目类别:
Molecular mechanisms of schizogony in malaria parasites
疟原虫分裂的分子机制
  • 批准号:
    10620476
  • 财政年份:
    2019
  • 资助金额:
    $ 75.31万
  • 项目类别:
Molecular mechanisms of schizogony in malaria parasites
疟原虫分裂的分子机制
  • 批准号:
    10161727
  • 财政年份:
    2019
  • 资助金额:
    $ 75.31万
  • 项目类别:
Molecular mechanisms of schizogony in malaria parasites
疟原虫分裂的分子机制
  • 批准号:
    10627871
  • 财政年份:
    2019
  • 资助金额:
    $ 75.31万
  • 项目类别:
Molecular mechanisms of schizogony in malaria parasites
疟原虫分裂的分子机制
  • 批准号:
    9797203
  • 财政年份:
    2019
  • 资助金额:
    $ 75.31万
  • 项目类别:
Molecular mechanisms of schizogony in malaria parasites
疟原虫分裂的分子机制
  • 批准号:
    10407023
  • 财政年份:
    2019
  • 资助金额:
    $ 75.31万
  • 项目类别:
Essential gene discovery in the malaria parasite Plasmodium falciparum
疟原虫恶性疟原虫中重要基因的发现
  • 批准号:
    8564839
  • 财政年份:
    2013
  • 资助金额:
    $ 75.31万
  • 项目类别:
Molecular characterization and substrate identification of malaria kinase PfCDPK5
疟疾激酶 PfCDPK5 的分子表征和底物鉴定
  • 批准号:
    8525534
  • 财政年份:
    2013
  • 资助金额:
    $ 75.31万
  • 项目类别:
Molecular analysis of a kinase essential for replication of Plasmodium falciparum
恶性疟原虫复制所必需的激酶的分子分析
  • 批准号:
    7868632
  • 财政年份:
    2010
  • 资助金额:
    $ 75.31万
  • 项目类别:

相似海外基金

The Language Environment in Fostering 5-Year-Old Children's Voluntary Involvements
培养5岁儿童自愿参与的语言环境
  • 批准号:
    22K13681
  • 财政年份:
    2022
  • 资助金额:
    $ 75.31万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
The Study of Reading Picture Books In 5-Year-Old Class and the Support Process of the Teachers
五岁班绘本阅读研究及教师支持过程
  • 批准号:
    19K14156
  • 财政年份:
    2019
  • 资助金额:
    $ 75.31万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Improving motor skills in 3-5 year old children with Autism Spectrum Disorder: Effects on the family unit.
提高患有自闭症谱系障碍的 3-5 岁儿童的运动技能:对家庭单位的影响。
  • 批准号:
    386469
  • 财政年份:
    2017
  • 资助金额:
    $ 75.31万
  • 项目类别:
    Studentship Programs
Epidemiological study and Creating new diagnostic methods for Neurodevelopmental disorders in 5-year-old children
5岁儿童神经发育障碍流行病学研究及诊断新方法
  • 批准号:
    16K10239
  • 财政年份:
    2016
  • 资助金额:
    $ 75.31万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Differences in motor milestone attainment in 4- and 5-year old children at risk for Developmental Coordination Disorder
有发育协调障碍风险的 4 岁和 5 岁儿童在运动里程碑方面的差异
  • 批准号:
    324425
  • 财政年份:
    2015
  • 资助金额:
    $ 75.31万
  • 项目类别:
Prevalence and social determinants of developmental outcomes among 5-year-old children with health disorders: A Pan-Canadian study
5 岁儿童健康障碍的患病率和发育结果的社会决定因素:一项泛加拿大研究
  • 批准号:
    322111
  • 财政年份:
    2015
  • 资助金额:
    $ 75.31万
  • 项目类别:
    Operating Grants
Fornative Expressive Behavior in Children's (4 years old and 5 year-old) Artistic Play Activities
儿童(4岁和5岁)艺术游戏活动中的本能表达行为
  • 批准号:
    26780506
  • 财政年份:
    2014
  • 资助金额:
    $ 75.31万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
The development which is a shift support program to a 1st grader of elementary school from 5-year old children who prevents "a 1st grade of elementary school, problem"
作为防止"小学一年级、问题"的5岁儿童到小学一年级学生的轮班支援计划的展开
  • 批准号:
    25381292
  • 财政年份:
    2013
  • 资助金额:
    $ 75.31万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Development of behavioural measures of sentence comprehension in 2 to 5 year old children
2至5岁儿童句子理解行为测量的发展
  • 批准号:
    449402-2013
  • 财政年份:
    2013
  • 资助金额:
    $ 75.31万
  • 项目类别:
    University Undergraduate Student Research Awards
Technology development and neuroimaging for 5 year old children with HIV infectio
5 岁 HIV 感染儿童的技术开发和神经影像学
  • 批准号:
    8333355
  • 财政年份:
    2011
  • 资助金额:
    $ 75.31万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了