Molecular mechanisms of schizogony in malaria parasites

疟原虫分裂的分子机制

基本信息

  • 批准号:
    9797203
  • 负责人:
  • 金额:
    $ 61.72万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-06-01 至 2024-05-31
  • 项目状态:
    已结题

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. Clinical malaria results from the asexual replication of parasites in human red blood cells. During the blood stage, P. falciparum replicates via schizogony, wherein daughter parasites are formed by a specialized cytokinesis known as segmentation. The inner membrane complex (IMC), a unique structure within the parasite composed of parasite proteins and a double lipid bilayer that is closely associated with the plasma membrane, and associated basal complex are hypothesized to orchestrate daughter parasite assembly and division. The focus of the current application is on the molecular mechanisms of schizogony and segmentation. Directed experiments will determine the biogenesis, composition, and function of the IMC and basal complex. We have discovered two novel parasites that are essential for schizogony and segmentation. The first, PfMOP, localizes initially near the centrosome and later to the apical end of the parasite and is critical for IMC biogenesis. The second, PfCINCH, localizes to the basal complex and is critical for parasite cytokinesis. These two proteins allow interrogation of the IMC and basal complex from the apical and basal ends of the parasite, respectively. The recently discovered P. falciparum Merozoite Organizing Protein is essential for both asexual and gametocyte development. In PfMOP-deficient parasites, the IMC does not form properly, resulting in a failure of segmentation, and the incompletely segmented merozoites remain in an agglomerate with a common cytoplasm. The molecular function of PfMOP and its link to the progression of schizogony and IMC biogenesis remain unknown. The proposed studies address these critical knowledge gaps. The first aim is divided into three independent subaims. In Aim 1.1, the link between PfMOP and IMC biogenesis in late schizogony will be investigated using a cell biologic approach with live video microscopy. In Aim 1.2, the function of PfMOP in early schizonts will be investigated, testing the hypothesis that PfMOP recruits a critical protein complex for chromosome condensation. In Aim 1.3, the PfMOP protein interactions in late schizonts will be determined, validated, and functionally evaluated by reverse-genetics. PfCINCH (Coordinator of nascent cell detachment) is a novel and essential component of the basal complex. In PfCINCH-deficient parasites, the final stages of segmentation are disrupted. In the second aim of this proposal, we focus on the cellular function of PfCINCH and its protein-protein interactions. The long-term objectives and public health implications of these studies are to identify critical biologic process pathways in the malaria parasite that could be targeted by future therapeutics.
项目总结

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:
    $ 61.72万
  • 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:
    $ 61.72万
  • 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:
    10584525
  • 财政年份:
    2022
  • 资助金额:
    $ 61.72万
  • 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:
    $ 61.72万
  • 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:
    $ 61.72万
  • 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:
    $ 61.72万
  • 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:
    $ 61.72万
  • 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:
    $ 61.72万
  • 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:
    $ 61.72万
  • 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:
    $ 61.72万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 61.72万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 61.72万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 61.72万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 61.72万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 61.72万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 61.72万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 61.72万
  • 项目类别:
    EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 61.72万
  • 项目类别:
    Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 61.72万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 61.72万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了