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Structural studies of the Apicomplexan glideosome-associated connector platform

Structural studies of the Apicomplexan glideosome-associated connector platform
顶端复合体滑翔体相关连接器平台的结构研究
批准号:
BB/W001764/1
负责人:
Steve Matthews
金额:
$69.31万
依托单位:
依托单位国家:
英国
项目类别:
Research Grant
财政年份:
2023
资助国家:
英国
项目状态:
未结题
起止时间:
2023 至 --

项目摘要

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中文摘要
翻译
寄生虫生长在不同的有机体中,虽然它通常对宿主没有好处,但它经常会导致疾病。Apicomplexan寄生虫是一种单细胞、类似动物的有机体,会在人类和动物中引起一系列疾病。值得注意的是,恶性疟原虫是致命疟疾的主要原因,而。弓形虫是世界上最常见的寄生虫之一,具有重要的兽医和医学价值,因为它可以导致流产或先天性疾病。它感染人类、野生动物和家畜,包括鸟、猫、绵羊、山羊、牛、猪和家禽。弓形虫病在全球范围内具有巨大的社会经济和健康影响。这些寄生虫生存的核心是它们独特的移动能力,这使得它们能够瞄准并入侵宿主细胞,生活在体内并随后逃脱。这些寄生虫物种用来进入和逃离它们的目标细胞的分子策略是相同的。在寄生虫体内,蛋白质的组装形成了一个分子机器,被称为滑小体。最近发现了一种新的蛋白质--胶质小体相关连接蛋白(GAC),它代表了宿主细胞和寄生虫细胞骨架之间的关键分子联系。这一立足点允许寄生虫相对于宿主细胞进行抓握和移动。本研究项目旨在研究胶质小体相关连接器(GAC)蛋白的分子形状和相互作用,并确定这个多组分系统的结构。这些信息将帮助我们在原子水平上了解这些寄生虫是如何移动的,由于这一过程对寄生虫的生存至关重要,它将为合理设计新的疫苗策略提供新的指导。
英文摘要
A parasite grows in a different organism and while it is usually not a benefit to the host, it can often cause disease. The Apicomplexan parasites are single-celled, animal-like organisms which cause a range of diseases in humans and animals. Notably, Plasmodium falciparum is the chief cause of fatal malaria, while. Toxoplasma gondii, one of the world's most common parasites, and is of veterinary and medical importance, as it can cause abortion or congenital disease. It infects humans, wild and domestic animals, including birds, cats, sheep, goats, cattle, pigs and poultry. Toxoplasmosis has an enormous socio-economic and health impacts across the globe. Central to the survival of these parasite is their distinct ability to move (be motile), which allows them to target and invade host cells, live inside and subsequent escape. The molecular strategies that these parasite species employ to enter and escape their target cells are shared. An assembly of proteins form a molecular machine inside the parasite, known as the glideosome. A new protein, the glideosome-associated connector (GAC) has been recently discovered which represents a crucial molecular link between the host cell and the parasite cellular skeleton. This foothold allows the parasite to grip and move with respect to the host cell.This research project aims investigate the molecular shapes and interactions of the glideosome-associated connector (GAC) protein and define the architecture of this multi-component system. This information will help us to see at the atomic level how these parasites can move, and as this process is essential for parasite survival it will provide new guidance for the rational design of new vaccine strategies.
期刊论文(2)
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会议论文
DOI: 10.1101/2023.01.23.525158
发表时间: 2023
期刊:
影响因子: --
作者: [Kumar A]
通讯作者: Kumar A
DOI: 10.7554/elife.86049
发表时间: 2023-04-04
期刊: eLife
影响因子: 7.7
作者: [Kumar A, Vadas O, Dos Santos Pacheco N, Zhang X, Chao K, Darvill N, Rasmussen HØ, Xu Y, Lin GM, Stylianou FA, Pedersen JS, Rouse SL, Morgan ML, Soldati-Favre D, Matthews S]
通讯作者: Matthews S
Understanding the structural basis of specificity in mitochondrial lipid transport and its role in drug resistance
  • 批准号:
    MR/S021191/1
  • 项目类别:
    Research Grant
  • 资助金额:
    $68.36万
  • 财政年份:
    2019
  • 负责人:
    Steve Matthews
  • 依托单位:
Structural basis of human TRIAP1/PRELI function in mitochondrial lipid transport and apoptosis
  • 批准号:
    MR/M019403/1
  • 项目类别:
    Research Grant
  • 资助金额:
    $55.34万
  • 财政年份:
    2015
  • 负责人:
    Steve Matthews
  • 依托单位:
Mechanism of poly-SUMO chain recognition by the ubiquitin ligase RNF4
  • 批准号:
    BB/J016799/1
  • 项目类别:
    Research Grant
  • 资助金额:
    $43.96万
  • 财政年份:
    2012
  • 负责人:
    Steve Matthews
  • 依托单位:
Regulating amyloid formation: structural studies of the secretion and assembly of 'curli' fibres
  • 批准号:
    G1001664/1
  • 项目类别:
    Research Grant
  • 资助金额:
    $49.76万
  • 财政年份:
    2011
  • 负责人:
    Steve Matthews
  • 依托单位:
国内基金
海外基金
脂滴聚集型小胶质细胞介导的髓鞘病变促进小鼠抑郁样行为及其机制研究
  • 批准号:
    82371528
  • 项目类别:
    面上项目
  • 资助金额:
    49.00万元
  • 批准年份:
    2023
  • 负责人:
    李媛
  • 依托单位:
星形胶质细胞介导的髓鞘吞噬参与慢性脑低灌注白质损伤的机制研究
  • 批准号:
    82371307
  • 项目类别:
    面上项目
  • 资助金额:
    49.00万元
  • 批准年份:
    2023
  • 负责人:
    汤耀辉
  • 依托单位: