Molecular Mechanisms of Organelle Formation in Bacteria

细菌细胞器形成的分子机制

• 批准号: 10624064
• 负责人: Arash Komeili
• 金额: $ 43.34万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10624064
• 关键词: Actins; Area; Bacteria; Biochemical; Biochemical Reaction; Biogenesis; Biologic Characteristic; Biological; Biological Assay; Biological Models; Biology; Cell membrane; Cell physiology; Cells; Chemicals; Contrast Media; Cytoskeleton; Development; Drug Delivery Systems; Engineering; Environment; Evolution; Genes; Genetic; Health; Hyperthermia; Individual; Iron; Knowledge; Lipid Bilayers; Lipid Binding; Magnetic Resonance Imaging; Magnetic nanoparticles; Magnetism; Microbe; Molecular; Names; Organelles; Organism; Output; Oxygen; Pathway interactions; Physiological; Prevalence; Process; Protein Sortings; Proteins; Research; Work; biomineralization; delivery vehicle; gut microbiome; interest; magnetosomes; member; membrane biogenesis; nanoscale; neoplastic cell; new therapeutic target; next generation; novel; opportunistic pathogen; particle; pathogenic bacteria; physical property; programs; rational design; targeted delivery; tumor

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.

与它们的真核生物类似，许多细菌物种使用脂质结合的细胞器， 执行必要的，有时是有毒的，以分区的方式生化反应。尽管 尽管它们对许多生物体的健康和生存的普遍性和重要性， 了解细菌细胞器的形成，功能和多样性。推进 在脂质结合细菌细胞器的机制研究中，我的小组开发了两种不同的模型 系统：趋磁细菌的磁小体和不同的铁小体室 厌氧微生物磁小体是细胞膜的脂质双层内陷， 蛋白质含量，在其中产生纳米尺寸的铁基磁性晶体。个人 磁小体在肌动蛋白样细胞骨架的帮助下排列成链，从而允许 趋磁细菌利用地磁场作为低氧环境的简单指南。的 磁小体的细胞生物学特征使其成为理解进化和分子生物学的理想工具。 细菌细胞器生物发生和生物矿化的基础。的磁性和物理性质 磁小体使它们成为生物医学应用开发的有吸引力的目标， 它们作为磁共振成像的造影剂、作为药物递送载体和作为介质的用途 用于高温杀死肿瘤细胞。最近，我的团队发现了一种新的铁积累 一种被称为铁小体的脂质细胞器。铁蛋白体是通过一个小的 许多基因，并发现在不同的细菌，包括居民成员的肠道微生物组 和机会致病菌。本提案中概述的研究计划将利用 和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，生化活动和细胞途径， 定义细菌细胞器的细胞生物学特征。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 和铁小体。第二，我们感兴趣的生化输出和细胞功能， 磁小体和铁小体。通过综合的遗传、化学和生理分析， 旨在了解这些细胞器是如何整合到其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。 这些方法的结合将揭示分子蓝图和进化多样性 细菌区室。在这个过程中，我们希望为合成再利用设计出更合理的途径。 磁小体和铁小体的工程设计，以在应用环境中更有效地部署它们。