RUI: Protein-Protein Interactions of Protein Kinase C During Polarized Growth in Filamentous Fungi

RUI:丝状真菌极化生长过程中蛋白激酶 C 的蛋白质-蛋白质相互作用

基本信息

  • 批准号:
    2222841
  • 负责人:
  • 金额:
    $ 63.92万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Continuing Grant
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-01-01 至 2025-12-31
  • 项目状态:
    未结题

项目摘要

This project seeks to increase our understanding of how fungi grow. Fungi are microorganisms which are used to produce commercially and medicinally valuable products, while others cause disease and result in major financial losses due to crop damage and spoilage of stored foods. Understanding their growth helps to advance technologies involving their use and aids in developing strategies to control their spread in harmful contexts. Fungi exist in two different forms; spherical, single-celled organisms and elongated, multicellular organisms, which are called filamentous fungi. This project focuses on growth and cell division in filamentous fungi. In order to grow and colonize their hosts, filamentous fungi extend into their environments by adding cellular materials at the tips of growing filaments, and they divide by constructing cross-walls, called septa, at evenly spaced intervals along the filaments. This project builds on previous NSF funded research in this laboratory which identified proteins involved in filamentous fungal growth and cell division, and began to determine which growth-related proteins form physical complexes that are involved in growth and division. Ongoing work will expand growth and cell division protein complexes by identifying new proteins which are involved, and it will further define how these complexes function. This research will be carried out by two senior scientists at Rhodes College (Memphis, TN) working with undergraduate students enrolled at Rhodes and students attending Historically Black Colleges in the Memphis region. Undergraduate students will be integrally involved in the work, and this research experience will strengthen their scientific education. This project investigates the function of protein kinase C in filamentous fungal growth and cell division (septation). Using the filamentous fungus Aspergillus nidulans as a model organism proteins involved in growth and cell division, including the A. nidulans homolog of protein kinase C, PkcA, have been identified. Previous research by the primary investigators of this project used techniques including in vivo microscopy of fluorescence labeled proteins, immunoprecipitations followed by mass spectrometry and proteomics analyses, and yeast two-hybrid assays to identify several proteins that physically interact with PkcA including the formin SepA, three Rho-type GTPase orthologs, a chitin synthase ortholog, a glucan synthase, and two important scaffold proteins - A. nidulans IQGAP ortholog SepG and an A. nidulans paxillin ortholog PaxB - which appear to have roles in PkcA’s localization to septation sites. This project will determine if these proteins or a subset are PkcA substrates, and if phosphorylation events play important roles in growth and cell division. The mechanisms by which PkcA protein complexes coalesce will be explored by identifying key domains of PkcA and complexed proteins that facilitate protein-protein interactions among them. Not only will this research be of value to the filamentous fungi community, but it will also benefit the broader cell biology community, as it will shed light on the factors that affect protein kinase C recruitment (and protein recruitment in general) to protein complexes and how protein networks function subsequent to recruitment.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
这个项目旨在增加我们对真菌如何生长的理解。真菌是用于生产商业和药用价值产品的微生物,而其他微生物则会引起疾病,并因作物受损和储存食品腐败而造成重大经济损失。了解它们的增长有助于推进涉及其使用的技术,并有助于制定控制其在有害环境中传播的战略。真菌以两种不同的形式存在:球形的单细胞生物和细长的多细胞生物,它们被称为丝状真菌。本项目主要研究丝状真菌的生长和细胞分裂。为了生长和定殖它们的宿主,丝状真菌通过在生长的丝状体的尖端添加细胞材料而延伸到它们的环境中,并且它们通过沿着丝状体以均匀间隔沿着的间隔构造横壁(称为隔膜)而分裂。该项目建立在该实验室先前NSF资助的研究基础上,该研究确定了参与丝状真菌生长和细胞分裂的蛋白质,并开始确定哪些生长相关蛋白质形成参与生长和分裂的物理复合物。正在进行的工作将通过识别参与其中的新蛋白质来扩展生长和细胞分裂蛋白质复合物,并将进一步定义这些复合物的功能。这项研究将由两名资深科学家在罗兹学院(孟菲斯,田纳西州)与本科生就读于罗兹和学生参加历史上黑人学院在孟菲斯地区。本科生将整体参与工作,这种研究经验将加强他们的科学教育。本计画探讨蛋白激酶C在丝状真菌生长与细胞分裂中的功能。以丝状真菌构巢曲霉(Aspergillus nidulans)为模式生物,研究了与生长和细胞分裂有关的蛋白质,包括A。已经鉴定了蛋白激酶C的构巢菌同系物PkcA。该项目的主要研究人员先前的研究使用了包括荧光标记蛋白质的体内显微镜,免疫沉淀随后质谱和蛋白质组学分析以及酵母双杂交测定的技术来鉴定与PkcA物理相互作用的几种蛋白质,包括PkcA SepA,三种Rho型GTbA直系同源物,几丁质合成酶直系同源物,葡聚糖合成酶和两种重要的支架蛋白- A。nidulans IQGAP直系同源物SepG和A.构巢菌桩蛋白直系同源物PaxB -其似乎在PkcA定位于分隔位点中起作用。该项目将确定这些蛋白质或其子集是否是PkcA底物,以及磷酸化事件是否在生长和细胞分裂中起重要作用。PkcA蛋白复合物聚结的机制将通过识别PkcA的关键结构域和促进它们之间蛋白质-蛋白质相互作用的复合蛋白来探索。这项研究不仅对丝状真菌群落有价值,而且还将有利于更广泛的细胞生物学群落,因为它将揭示影响蛋白激酶C募集的因素,(一般蛋白质募集)该奖项反映了NSF的法定使命,并已被认为是值得通过评估使用的支持,基金会的学术价值和更广泛的影响审查标准。

项目成果

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Terry Hill其他文献

Terry Hill的其他文献

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{{ truncateString('Terry Hill', 18)}}的其他基金

RUI: Subcellular Targeting of Protein Kinase C and a Novel Membrane Protein in Polarized Growth of Aspergillus nidulans
RUI:蛋白激酶 C 和新型膜蛋白在构巢曲霉极化生长中的亚细胞靶向
  • 批准号:
    0742907
  • 财政年份:
    2008
  • 资助金额:
    $ 63.92万
  • 项目类别:
    Standard Grant
C-RUI: Identification of Genes Regulating Cell Wall Integrity in Aspergillus nidulans
C-RUI:构巢曲霉细胞壁完整性调节基因的鉴定
  • 批准号:
    0211600
  • 财政年份:
    2003
  • 资助金额:
    $ 63.92万
  • 项目类别:
    Continuing Grant

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相似海外基金

Collaborative Research: RUI: An In-depth Characterization of Divalent Cadmium Binding to Human Cardiac Troponin C and the Impact on Subsequent Protein Interactions
合作研究:RUI:二价镉与人心肌肌钙蛋白 C 结合的深入表征以及对后续蛋白质相互作用的影响
  • 批准号:
    2203467
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    $ 63.92万
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    Standard Grant
Collaborative Research: RUI: An In-depth Characterization of Divalent Cadmium Binding to Human Cardiac Troponin C and the Impact on Subsequent Protein Interactions
合作研究:RUI:二价镉与人心肌肌钙蛋白 C 结合的深入表征以及对后续蛋白质相互作用的影响
  • 批准号:
    2203466
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    2022
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    $ 63.92万
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    Standard Grant
RUI: Understanding how de novo evolved genes evolve protein interactions and regulatory mechanisms in Drosophila reproduction
RUI:了解果蝇繁殖中从头进化的基因如何进化蛋白质相互作用和调节机制
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    2212972
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    2022
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    $ 63.92万
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RUI: Understanding Cu(I) Interactions with Zinc-Metalloproteins: Impact of Cu(I) on Structure and Function of the X-Linked Inhibitor of Apoptosis Protein
RUI:了解 Cu(I) 与锌金属蛋白的相互作用:Cu(I) 对 X 连锁凋亡蛋白抑制剂结构和功能的影响
  • 批准号:
    1807773
  • 财政年份:
    2018
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    $ 63.92万
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    Standard Grant
RUI: Collaborative Research: Understanding the protein-polysaccharide interactions of natural composite materials in one and two dimensions
RUI:合作研究:了解天然复合材料的一维和二维蛋白质-多糖相互作用
  • 批准号:
    1809541
  • 财政年份:
    2018
  • 资助金额:
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  • 项目类别:
    Continuing Grant
RUI: Collaborative Research: Understanding the protein-polysaccharide interactions of natural composite materials in one and two dimensions
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  • 批准号:
    1809354
  • 财政年份:
    2018
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    $ 63.92万
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RUI: Domain-Domain and Protein-Protein Interactions in Reactive Oxygen Species
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    1608484
  • 财政年份:
    2016
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    $ 63.92万
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RUI: NMR Investigation of the Role of Protein Dynamics in the Selective Interactions between RGS and Galpha Signaling Proteins
RUI:蛋白质动力学在 RGS 和 Galpha 信号蛋白选择性相互作用中作用的 NMR 研究
  • 批准号:
    1158177
  • 财政年份:
    2012
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RUI: Role of CP43 in Protein/Protein & Protein/Cofactor Interactions in Photosystem II
RUI:CP43 在蛋白质/蛋白质中的作用
  • 批准号:
    0517166
  • 财政年份:
    2005
  • 资助金额:
    $ 63.92万
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RUI: Protein-Protein Interactions Mediating Substrate Recognition by the VirB Complex of Agrobacterium Tumefaciens
RUI:介导根癌农杆菌 VirB 复合物识别底物的蛋白质-蛋白质相互作用
  • 批准号:
    0049006
  • 财政年份:
    2000
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