Self-nonself recognition and multicellularity in myxobacteria

粘细菌的自我非自我识别和多细胞性

基本信息

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
项目类别：
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

项目摘要

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.

抽象的生物学中的一个基本问题是多细胞生物体中的单个细胞如何将其他细胞视为自我，在组织、器官和整个个体中协同发挥作用。为了解决这个复杂的问题，我们研究了一个相对简单且可通过实验追踪的方法模型生物，黄色粘球菌（Myxococcus xanthus）虽然是一种细菌，但黄色粘球菌（Myxococcus xanthus）表现出许多特征。存在于组织和更复杂的多细胞物种中，其中一个特征是多细胞发育。我们发现，另一个特征是细胞区分饥饿的能力。自我和非自我的细胞蛋白质和脂质的交换是由a介导的。称为 TraA 的多态性细胞表面受体及其伙伴 TraB 仅具有相同的细胞。或几乎相同的 TraA 受体通过同型相互作用产生社会结果。称为外膜交换 (OME) 的过程根据膜的特性而变化。在某些情况下，OME 会导致细胞相互作用，从而产生健康的供体。在其他情况下，OME 会通过补充细胞成分来修复受损细胞。当配对细胞不是克隆时，多态性毒素会产生拮抗作用。转移至缺乏同源免疫的受体细胞。我们未来的目标是多方面的，包括了解 OME，以及更广泛地说，如何在接下来的五年里，我们将批判性地认识细胞自我并过渡到多细胞性。研究 OME 如何导致合作性，其中一个研究领域是 TraA/B 如何指导。人群中的紧急行为，包括同步和协调的运动。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正在用生物传感器研究控制细胞同步的转导途径。其他方法将探测 M. xanthus 的反应和变化。适应环境压力，从而将这些适应能力转移到天真的人群中 OME 的第二个研究领域解决了粘细菌如何迅速分化成不同的细菌。我们的初步研究结果表明，水平基因。非裂解性转导颗粒的转移通过携带多态性介导群体分化第三个重点领域将阐明 OME 的机制。最后，我们将探索自我融合的新机制。识别及其在多细胞生命中的作用。