Emergent metabolic coordination and cell-to-cell signaling in bacterial biofilms-ADMIN SUPP for Equipment

项目总结 了解细菌之间的交流是一个重要的基本生物学问题 对公众健康的影响，特别是在被称为生物膜的细菌群落的背景下。而当 细菌是单细胞生物，生物膜可以通过 紧急协调和动态的细胞间信号传递。这种生物膜特有的集体行为 有助于他们耐受抗生素，并在几乎任何环境中茁壮成长。当……到来的时候 下一代测序带来了对广泛和无处不在的角色的新的理解 自然界中的细菌，我们对其群落协调的分子机制的理解仍然存在 在它的初级阶段。我的首要目标是了解细菌是如何产生协调的群体行为的 生物膜群落通过以前未探索的细胞间信号机制，以及这些机制是如何 突发行为带来了社区层面的实用利益。具体地说，在未来五年， 我的团队将使用多尺度显微镜、高通量方法和数量遗传学来 解读基因调节、新陈代谢适应和微环境反馈如何引起 细菌生物膜中的紧急配位和多细胞行为。有了这个米拉奖，我的团队 我将通过关注枯草杆菌生物膜模型来探索这些问题，我们最近在那里使用了一种 多尺度微流控平台发现生物膜细菌可参与离子通道介导 细胞间的电化学信号传递。这一发现以及其他未发表的现象 由我的团队发现，使枯草杆菌成为一个研究突发行为的强大系统 产生于细菌生物膜中，来自单细胞水平的特性，如基因调控网络和 代谢适应。我们的数据将为多细胞现象的定量模型提供信息，这将 让我们从系统层面了解微生物中的多细胞行为，并提出新的 控制生物膜的方法。

PROJECT SUMMARY Understanding communication among bacteria is a fundamental biological problem with critical implications for public health, especially in the context of bacterial communities known as biofilms. While bacteria are single-celled organisms, biofilms can exhibit many multicellular behaviors through emergent coordination and dynamic cell-to-cell signaling. Such collective behaviors unique to biofilms contribute to their ability to tolerate antibiotics and thrive in nearly any environment. While the advent of next-generation sequencing has ushered in a new appreciation for the broad and ubiquitous roles of bacteria in nature, our understanding of their molecular mechanisms of community coordination remains in its infancy. My overarching goal is to understand how coordinated group behaviors arise in bacterial biofilm communities through previously unexplored cell-to-cell signaling mechanisms, and how these emergent behaviors impart functional community-level benefits. Specifically, over the next five years, my group will use multiscale microscopy, high-throughput approaches, and quantitative genetics to decipher how gene regulation, metabolic adaptation, and microenvironmental feedback give rise to emergent coordination and multicellular behaviors in bacterial biofilms. With this MIRA award, my group will explore these questions by focusing on model Bacillus subtilis biofilms, where we recently used a multiscale microfluidic platform to discover that biofilm bacteria can engage in ion channel-mediated electrochemical cell-to-cell signaling. This discovery, along with other unpublished phenomena discovered by my group, make B. subtilis a powerful system for investigating how emergent behaviors arise in bacterial biofilms from single-cell-level properties such as gene regulatory networks and metabolic adaptation. Our data will inform quantitative models of multicellular phenomena, which will give us a system-level understanding of multicellular behaviors in microbes, as well as suggesting new ways to control biofilms.