Elucidation of the first interspecies chemical signaling mechanisms in Capsaspora owczarzaki--the predator of a human pathogen and a model for the evolution of animal multicellularity

阐明 Capsaspora owczarzaki 中的第一个种间化学信号传导机制——人类病原体的捕食者和动物多细胞进化的模型

基本信息

  • 批准号:
    10028844
  • 负责人:
  • 金额:
    $ 38.93万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-07-01 至 2025-04-30
  • 项目状态:
    未结题

项目摘要

Project Summary / Abstract Capsaspora owczarzaki is a protozoan that may control a neglected tropical disease and reveal the earliest animal cell-cell signaling mechanisms. However, little is known about this organism at a chemical level. Capsas- pora lives inside Biomphalaria snails (the vectors that transmit schistosome worms that cause schistosomiasis). Capsaspora hunts and kills schistosomes, making it a promising biocontrol agent. However, no one knows which molecules Capsaspora senses to colonize its snail host, nor how it senses its schistosome prey. Furthermore, Capsaspora is one of the closest living relatives of animals, with which it shares signaling and adhesion genes. It exhibits reversible aggregation and chemotaxis, reminiscent of human neural crest cells, immune cells, and metastatic cancer cells. Therefore, it is a phylogenetically relevant model to study how multicellular phenotypes in animals evolved and act in healthy and disease states. However, no one has found which molecules regulate Capsaspora’s adhesion and chemotaxis phenotypes to determine if its mechanisms are conserved with those in animals. For Capsaspora to reach its potential as a biocontrol agent and to reveal insight into the evolution of animal multicellularity, its mechanisms of chemical signaling must be uncovered. The proposed research program will discover the molecular mechanisms that regulate two phenotypes, each of which is relevant both to killing schistosomes and to understanding the evolution of multicellular traits in animals. First, Capsaspora forms aggregates in response to snail serum, which is notable for two reasons: (1) it is the only Capsaspora response to a snail host factor, presumably enabling Capsaspora to recognize its snail host environment, and (2) it is the only regulated cell-cell adhesion process in Capsaspora, which is the only non- animal with complete integrin and cadherin adhesion complexes. Therefore, discovery of the mechanism of se- rum-induced aggregation may reveal both how Capsaspora colonizes its host and whether or not regulated animal cellular adhesion mechanisms were active in animals’ common ancestor. Second, Capsaspora migrates toward schistosome prey, which is notable for two reasons: (1) it is the only known avenue by which Capsaspora senses schistosomes, and (2) it is the only reported chemotaxis behavior in the closest relatives of animals (the holozoans). Therefore, discovery of the chemoattractant and response may reveal how Capsaspora hunts schis- tosomes and whether or not animal chemotaxis mechanisms were active in animals’ common ancestor. In both projects, the cue molecule and the Capsaspora receptor will be identified. Subsequent work will decipher how the signal is transduced. Finally, the significance of these phenotypes for snail colonization and schistosome killing will be tested in vivo, and the evolutionary conservation of these signaling mechanisms with present-day animals will be examined. Discovery of the signals and mechanisms that trigger Capsaspora aggregation and chemotaxis may reveal essential traits for Capsaspora to decrease schistosomiasis infections. Furthermore, this work may reveal the most fundamental mechanisms of regulated multicellularity in animals.
项目总结/摘要 Capsaspora owczarzaki是一种原生动物,可能控制一种被忽视的热带疾病,并揭示了最早的 动物细胞间信号传导机制。然而,在化学水平上对这种生物知之甚少。Capsas- 孢子虫生活在双脐螺(一种传播引起血吸虫病的蠕虫虫的媒介)体内。 Capsaspora能捕食和杀死寄生虫,使其成为一种很有前途的生物防治剂。然而,没有人知道 Capsaspora感觉到的分子殖民它的蜗牛宿主,也不知道它如何感觉到它的猎物。此外,委员会认为, Capsaspora是动物的近亲之一,它与动物共享信号和粘附基因。 它表现出可逆的聚集和趋化性,使人联想到人类神经嵴细胞,免疫细胞, 转移性癌细胞因此,这是一个与遗传学相关的模型,以研究多细胞表型如何 在动物进化和行动在健康和疾病状态。然而,没有人发现哪些分子调节 Capsaspora的粘附和趋化表型,以确定其机制是否与 动物对于Capsaspora来说,要发挥其作为生物防治剂的潜力,并揭示其进化的洞察力, 动物的多细胞性,其化学信号的机制必须被揭示。 拟议的研究计划将发现调节两种表型的分子机制, 这与杀死多细胞体和理解动物中多细胞性状的进化有关。 首先,Capsaspora响应于蜗牛血清而形成聚集体,这是值得注意的,原因有两个:(1)它是 只有Capsaspora对蜗牛宿主因子的反应,可能使Capsaspora能够识别其蜗牛宿主 (2)它是Capsaspora中唯一受调节的细胞-细胞粘附过程,这是Capsaspora中唯一不受调节的细胞-细胞粘附过程。 具有完整整合素和钙粘蛋白粘附复合物的动物。因此,研究硒的作用机制, 朗姆酒诱导的聚集可能揭示Capsaspora如何在其宿主中定殖以及是否受到调节 动物细胞粘附机制在动物的共同祖先中是活跃的。第二,Capsaspora (1)这是唯一已知的途径,Capsaspora (2)它是唯一报道的在动物近亲中的趋化行为( 完整动物)。因此,化学引诱物和反应的发现可能揭示Capsaspora如何狩猎schis- 以及动物的趋化机制在动物的共同祖先中是否活跃。 在这两个项目中,将确定线索分子和Capsaspora受体。后续工作将破译 信号是如何传递的最后,这些表型对于蜗牛定殖和寄生体的意义 杀死将在体内进行测试,这些信号传导机制的进化保守性与当今的 将对动物进行检查。发现触发Capsaspora聚集的信号和机制, 趋化性可能揭示了Capsaspora减少血吸虫感染的基本特征。而且这 这项工作可能揭示动物中调节多细胞性的最基本机制。

项目成果

期刊论文数量(0)
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Joseph P. Gerdt其他文献

Streptomyces secretes a siderophore that sensitizes competitor bacteria to phage infection
链霉菌分泌一种铁载体,使竞争细菌对噬菌体感染敏感
  • DOI:
    10.1038/s41564-024-01910-8
  • 发表时间:
    2025-01-08
  • 期刊:
  • 影响因子:
    19.400
  • 作者:
    Zhiyu Zang;Chengqian Zhang;Kyoung Jin Park;Daniel A. Schwartz;Ram Podicheti;Jay T. Lennon;Joseph P. Gerdt
  • 通讯作者:
    Joseph P. Gerdt

Joseph P. Gerdt的其他文献

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{{ truncateString('Joseph P. Gerdt', 18)}}的其他基金

Elucidation of the first interspecies chemical signaling mechanisms in Capsaspora owczarzaki--the predator of a human pathogen and a model for the evolution of animal multicellularity
阐明 Capsaspora owczarzaki 中的第一个种间化学信号传导机制——人类病原体的捕食者和动物多细胞进化的模型
  • 批准号:
    10797148
  • 财政年份:
    2020
  • 资助金额:
    $ 38.93万
  • 项目类别:
Elucidation of the first interspecies chemical signaling mechanisms in Capsaspora owczarzaki--the predator of a human pathogen and a model for the evolution of animal multicellularity
阐明 Capsaspora owczarzaki 中的第一个种间化学信号传导机制——人类病原体的捕食者和动物多细胞进化的模型
  • 批准号:
    10613475
  • 财政年份:
    2020
  • 资助金额:
    $ 38.93万
  • 项目类别:
Elucidation of the first interspecies chemical signaling mechanisms in Capsaspora owczarzaki--the predator of a human pathogen and a model for the evolution of animal multicellularity
阐明 Capsaspora owczarzaki 中的第一个种间化学信号传导机制——人类病原体的捕食者和动物多细胞进化的模型
  • 批准号:
    10393683
  • 财政年份:
    2020
  • 资助金额:
    $ 38.93万
  • 项目类别:
Elucidation of the first interspecies chemical signaling mechanisms in Capsaspora owczarzaki--the predator of a human pathogen and a model for the evolution of animal multicellularity
阐明 Capsaspora owczarzaki 中的第一个种间化学信号传导机制——人类病原体的捕食者和动物多细胞进化的模型
  • 批准号:
    10204061
  • 财政年份:
    2020
  • 资助金额:
    $ 38.93万
  • 项目类别:

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