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
• 负责人: Joseph P. Gerdt
• 金额: $ 24.99万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/10797148
• 关键词: Acceleration; Adhesions; Animals; Biochemistry; Biocontrols; Biological Assay; C10; Cell Aggregation; Cells; Cellularity; Chemicals; Communicable Diseases; Computer software; Disease; Dose; Educational process of instructing; Equipment; Eukaryota; Evolution; Experimental Designs; Fluorescence; Fractionation; Genes; Grant; Image; Incubators; Libraries; Life; Manuals; Microbe; Modeling; Nature; Optics; Parasites; Phase; Phenotype; Phylogenetic Analysis; Reproducibility; Research Personnel; Schedule; Schistosoma; Schistosomiasis; Signal Induction; Signal Transduction; Signaling Molecule; Snails; Specialist; Symbiosis; Testing; Time; cytate; design; experimental study; host microbiome; human pathogen; imager; inhibitor; instrument; microbial; migration; mutant; neglect; neglected tropical diseases; parent project; pharmacologic; prevent; response; screening; vector transmission

Summary/Abstract Protists are frequently involved in neglected infectious diseases, and they teach us about the evolutionary origins of multicellular life and host-microbiome interactions. The parent project supports our studies to uncover the molecules and mechanisms that drive interspecies chemical signaling in the protist Capsaspora owczarzaki and its close relatives. Capsaspora is naturally found in the snail vectors that transmit the parasites that cause schistosomiasis. Capsaspora hunts and kills schistosomes, making it a potential biocontrol agent against this neglected tropical disease. However, no one knows which molecules Capsaspora senses to colonize its snail host, nor how it senses its schistosome prey. Furthermore, Capsaspora and other unicellular holozoans are the closest living relatives of animals, with which they share signaling and adhesion genes. Therefore, these protists are phylogenetically relevant models to study how multicellular phenotypes and microbial symbioses in animals evolved and act in healthy and disease states. As specialists in the biochemistry of interspecies interactions, we are characterizing the molecules and mechanisms that drive Capsaspora’s interactions with snails and schistosomes, as well the interactions of related protists with neighboring microbes. Time-lapse imaging is required to investigate most of the signal-induced phenotypes that we study. Furthermore, we rely on testing dozens to thousands of different conditions in experiments employing bioassay-guided fractionation of metabolite mixtures, dose-response assays of pharmacological inhibitors, and screening of mutant libraries. Given these needs of several researchers on this project, I am requesting a BioTek Cytation C10 imager with BioSpa incubator/scheduler. This instrument replaces a retired high- content imager that is no longer serviceable. The requested instrument is explicitly designed for the medium- throughput live-cell time-course imaging that we require. It will be equipped with phase and confocal fluorescence optics, and it will include software for rapid analysis of cell aggregation, migration, and fluorescence. It will feature simultaneous time-lapse imaging of eight microtiter plates, which will prevent scheduling conflicts that delay experiments. Additionally, it will allow single users to perform large-scale screens that are impossible with our current instruments. Furthermore, by spending less time manually collecting images, we can devote more time to designing experiments and developing hypotheses. Finally, the automated nature of the instrument will increase reproducibility of experiments between researchers. This equipment will be an essential workhorse instrument for all researchers working on this grant. It will expand and accelerate our chemical signaling discoveries that may both inform the use of a new biocontrol agent and reveal core mechanisms of regulated multicellularity in animals.

总结/摘要 原生生物经常与被忽视的传染病有关，它们告诉我们进化的过程。 多细胞生命的起源和宿主-微生物组相互作用。母项目支持我们的研究， 揭示驱动原生生物Capsaspora种间化学信号的分子和机制 奥恰尔扎基及其近亲。Capsaspora天然存在于传播病毒的蜗牛载体中。 引起血吸虫病的寄生虫Capsaspora狩猎并杀死寄生虫，使其成为潜在的 对抗这种被忽视的热带疾病的生物控制剂。然而，没有人知道哪些分子 Capsaspora感觉到它的蜗牛宿主，也不知道它如何感觉到它的麻烦的猎物。此外，委员会认为， Capsaspora和其他单细胞全虫是动物的近亲，它们与动物共享 信号和粘附基因。因此，这些原生生物是研究如何 动物的多细胞表型和微生物共生体在健康和疾病状态下进化并发挥作用。 作为物种间相互作用的生物化学专家，我们正在描述分子和 驱动Capsaspora与蜗牛和寄生虫相互作用的机制，以及 与邻近微生物相关的原生生物。 我们研究的大多数信号诱导的表型都需要延时成像来研究。 此外，我们依赖于在实验中测试数十到数千种不同的条件， 代谢物混合物的生物测定引导分级，药理学抑制剂的剂量反应测定， 和突变体文库的筛选。考虑到这个项目的几个研究人员的这些需求，我请求 BioTek Cytation C10成像仪，配有BioSpa培养箱/调度器。这台仪器取代了一台退役的高... 不再可用的内容成像器。所要求的仪器是专门为介质设计的- 活细胞时间进程成像的能力。它将配备相位和共焦 它将包括用于快速分析细胞聚集、迁移和 荧光。它将同时对8个微量滴定板进行延时成像， 调度冲突，延迟实验。此外，它将允许单个用户执行大规模 用我们现有的仪器是不可能的。此外，通过手动花费更少的时间 收集图像，我们可以投入更多的时间来设计实验和发展假设。最后， 该仪器的自动化性质将提高研究人员之间实验的可重复性。这 设备将是所有研究人员在这项赠款工作中必不可少的工具。将扩大 并加速我们的化学信号发现，这可能会为新的生物防治剂的使用提供信息， 揭示了动物中调节多细胞性的核心机制。

项目成果

Chemical factors induce aggregative multicellularity in a close unicellular relative of animals.

• DOI: 10.1073/pnas.2216668120
• 发表时间: 2023-05-02
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Ros-Rocher, Nuria;Kidner, Ria Q.;Gerdt, Catherine;Davidson, W. Sean;Ruiz-Trillo, Inaki;Gerdt, Joseph P.
• 通讯作者: Gerdt, Joseph P.

Host lipids regulate multicellular behavior of a predator of a human pathogen.

宿主脂质调节人类病原体捕食者的多细胞行为。

• DOI: 10.1101/2024.01.31.578218
• 发表时间: 2024
• 期刊: bioRxiv : the preprint server for biology
• 作者: Kidner,RiaQ;Goldstone,EleanorB;Laidemitt,MartinaR;Sanchez,MelissaC;Gerdt,Catherine;Brokaw,LorinP;Ros-Rocher,Núria;Morris,Jamie;Davidson,WSean;Gerdt,JosephP
• 通讯作者: Gerdt,JosephP