Self-nonself recognition and multicellularity in myxobacteria

粘细菌的自我非自我识别和多细胞性

• 批准号: 10597640
• 负责人: DANIEL WALL
• 金额: $ 36.13万
• 依托单位: UNIVERSITY OF WYOMING
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10597640
• 关键词: Address; Area; Bacteria; Behavior; Biology; Biosensor; Cell Communication; Cell Surface Receptors; Cells; Cellular Structures; Cellularity; Complex; Discrimination; Environment; Exhibits; Future; Genes; Goals; Horizontal Gene Transfer; Immune system; Immunity; Individual; Investigation; Life; Lipids; Mediating; Membrane; Membrane Fusion; Monitor; Movement; Myxococcales; Myxococcus xanthus; Nonlytic; Organ; Organism; Population; Process; Property; Proteins; Research; Role; Signal Transduction Pathway; Social Discrimination; Social outcome; Starvation; Tissues; Toxin; antagonist; cancer cell; cell assembly; cell behavior; cell injury; cell motility; cellular development; environmental stressor; model organism; particle; pathogen; receptor; release of sequestered calcium ion into cytoplasm; repaired; response; social group; trait; transcriptome

Abstract A fundamental question in biology is how individual cells within a multicellular organism recognize other cells as self to cooperatively function in tissues, organs and as whole individuals. To address this complex question, we study a relatively simple and experimentally trackable model organism, Myxococcus xanthus. Although a bacterium, M. xanthus exhibits many traits found in tissues and more complex multicellular species. One trait is multicellular development in response to starvation. Another trait, we discovered, is the ability of cells to distinguish between self and nonself for the exchange of cellular proteins and lipids. Recognition is mediated by a polymorphic cell surface receptor called TraA and its partner TraB. Only cells that bear identical or nearly identical TraA receptors engage by homotypic interactions. Social outcomes from this process, called outer membrane exchange (OME), vary depending on the properties of the interacting cells. In some cases, OME leads to cooperative interactions whereby healthy donors repair damaged cells by replenishing their cell components. In other cases, OME leads to antagonism when partnering cells are not clonal. Discrimination occurs by polymorphic toxin transfer to recipient cells that lack cognate immunity. Our future goals are multifaceted with respect to understanding OME and, more broadly, how cells recognize self and transition toward multicellularity. Over the next five years we will critically examine how OME leads to cooperativity. One area of investigation is how TraA/B directs emergent behaviors in populations that include synchronized and coordinated movements. This will be explored by monitoring global gene expression and how TraA/B interacts with a signal transduction pathway that controls motility. Cell synchronization is being studied with a biosensor the monitors’ calcium fluxes in cells. Other approaches will probe how M. xanthus responds and adapts to environmental stresses, whereby those adaptations are transferred to naïve populations by OME. A second area of research addresses how myxobacteria rapidly diverge into different social groups in natural environments. Our preliminary findings indicate that horizontal gene transfer by non-lytic transducing particles mediate population divergence by carrying polymorphic genes involved in social discrimination. A third focus area will elucidate the mechanism of OME thought to involve outer membrane fusion. Finally, we will explore new mechanisms of self- recognition and its role in multicellular life.

抽象的 生物学的一个基本问题是多细胞组织中的个体细胞如何 将其他细胞识别为自我在组织，器官和整个个体中协调起作用。 为了解决这个复杂的问题，我们研究了一个相对简单且可追踪的 模型有机体，粘液虫Xanthus。尽管细菌，M。Xanthus表现出许多特征 在组织和更复杂的多细胞物种中发现。一个特征是多细胞的发展 对饥饿的反应。我们发现，另一个特征是细胞区分区分的能力 自我和非自我交换细胞蛋白和脂质。识别是由 多态细胞表面受体称为Traa及其伴侣手提布。只有相同的细胞 或几乎相同的Traa接收器通过同型相互作用所吸引。社会成果 工艺称为外膜交换（OME），取决于 相互作用的细胞。在某些情况下，OME会导致合作互动，使健康捐助者 通过复制其细胞成分来修复受损的细胞。在其他情况下，OME会导致 伴侣细胞时的拮抗作用不是克隆。歧视是由多态性毒素发生的 转移到缺乏同源免疫力的受体细胞中。 关于理解OME，更广泛地了解我们未来的目标是多方面的 细胞识别自我和向多细胞的过渡。在接下来的五年中，我们将批判性 检查OME如何导致合作。调查领域是Traa/b如何指导 人群中的紧急行为包括同步和协调运动。这 将通过监测全局基因表达以及Traa/B如何与信号相互作用来探索 控制运动的转导途径。细胞同步正在研究生物传感器 监测细胞中的钙通量。其他方法将探讨Xanthus的响应和 适应环境压力，从而将这些适应转移到幼稚的人群中 由Ome。第二个研究领域介绍了粘霉菌如何迅速脱离不同 自然环境中的社会群体。我们的初步发现表明水平基因 通过携带多态性介导种群差异，通过非透明转导颗粒介导种群差异 涉及社会歧视的基因。第三个焦点区域将阐明OME的机制 被认为涉及外膜融合。最后，我们将探索自我的新机制 认可及其在多细胞生活中的作用。