Molecular Mechanisms of Organelle Formation in Bacteria

就像它们的真核生物一样，许多细菌物种利用脂质结合的细胞器 以一种分隔的方式执行必要的、有时是有毒的生化反应。尽管 它们的流行和对许多有机体的健康和生存的重要性相对较少 了解细菌细胞器的形成、功能和多样性。要推进 脂质结合细菌细胞器的机制研究，我的团队发展了两个不同的模型 系统：趋磁细菌的磁小体和不同种类的铁质隔间 厌氧微生物。磁小体是细胞膜的脂双层内陷，具有独特的 蛋白质含量，在此范围内产生纳米尺寸的铁基磁性晶体。个体 在肌动蛋白样细胞骨架的帮助下，磁小体排列成链，从而允许 趋磁细菌使用地磁场作为低氧环境的简单指南。这个 磁小体的细胞生物学特性使其成为了解进化和分子的理想工具 细菌中细胞器的生物发生和生物矿化的基础。它的磁性和物理性质 磁小体使其成为开发生物医学应用的有吸引力的目标，包括 它们用作磁共振成像的造影剂、药物输送载体和介质 用于高温杀灭肿瘤细胞。最近，我的团队发现了一种新的蓄铁方法 脂质结合的细胞器称为铁体。铁小体是通过一个小分子的作用形成的 基因的数量，并在各种细菌中发现，包括肠道微生物组的常驻成员 和机会主义的病原体。本提案中概述的研究计划将利用专业知识 和我的团队中现有的知识来探索磁小体和铁小体的三个一般领域 生物学。首先，我们将研究分子组成、生化活性和细胞途径 定义细菌细胞器的细胞生物学特性。我们目前的重点是了解 磁小体的膜生物发生、蛋白质分选和亚细胞排列机制 和铁体。第二，我们对生物化学产量和细胞功能感兴趣。 磁小体和铁小体。使用全面的遗传、化学和生理分析，我们 目的了解这些细胞器是如何整合到宿主的基本功能中的 有机体。第三，我们希望利用磁小体和铁小体形成的自然多样性。 了解细菌细胞器形成的共同和独特的进化路径。 这些方法的结合将阐明分子蓝图和进化多样性。 细菌隔间。在这个过程中，我们希望设计出更合理的综合再利用路径。 对磁小体和铁小体进行工程设计，以便在应用环境中更有效地部署它们。

Much like their eukaryotic counterparts, numerous bacterial species use lipid-bounded organelles to execute essential, and at times toxic, biochemical reactions in a compartmentalized fashion. Despite their prevalence and importance to the health and survival of many organisms, relatively little is understood regarding the formation, function, and diversity of bacterial organelles. To advance the mechanistic study of lipid-bounded bacterial organelles, my group has developed two distinct model systems: magnetosomes of magnetotactic bacteria and the ferrosome compartments of diverse anaerobic microbes. Magnetosomes are lipid-bilayer invaginations of the cell membrane with a unique protein content, within which nanometer-sized iron-based magnetic crystals are produced. Individual magnetosomes are arranged into a chain with the help of an actin-like cytoskeleton, thus allowing magnetotactic bacteria to use geomagnetic fields as a simple guide for low oxygen environments. The cell biological features of magnetosomes make them ideal for understanding the evolution and molecular basis of organelle biogenesis and biomineralization in bacteria. The magnetic and physical properties of magnetosomes make them attractive targets for the development of biomedical applications including their use as contrast agents for magnetic resonance imaging, as drug delivery vehicles and as a medium for hyperthermic killing of tumor cells. More recently, my group has discovered a novel iron-accumulating lipid-bounded organelle named the ferrosome. Ferrosomes are formed through the action of a small number of genes and are found in diverse bacteria including resident members of the gut microbiome and opportunistic pathogens. The research program outlined in this proposal will leverage the expertise and existing knowledge within my group to explore three general areas of magnetosome and ferrosome biology. First, we will study the molecular components, biochemical activities, and cellular pathways that define the cell biological characteristics of bacterial organelles. Our current focus is to understand the mechanisms of membrane biogenesis, protein sorting, and subcellular arrangement for magnetosomes and ferrosomes. Second, we are interested in the biochemical output and cellular function of magnetosomes and ferrosomes. Using comprehensive genetic, chemical, and physiological assays we aim to understand how these organelles are integrated into the essential functions of their host organisms. Third, we look to exploit the natural diversity of magnetosome- and ferrosome-forming organisms to understand the common and unique evolutionary paths of organelle formation in bacteria. The combination of these approaches will shed light on the molecular blueprint and evolutionary diversity of bacterial compartments. In the process, we hope to devise more rational paths for synthetic re- engineering of magnetosomes and ferrosomes to deploy them more effectively in applied settings.