Mapping the Interactions and Dynamics that Organize Bacteria Cells

绘制细菌细胞组织的相互作用和动态图

• 批准号: 10630966
• 负责人: Julie Biteen
• 金额: $ 30.73万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10630966
• 关键词: Address; Bacteria; Bacterial Model; Bacteriology; Biochemical Reaction; Biochemistry; Biology; Biophysics; Caulobacter crescentus; Cell physiology; Cells; Cellular biology; Color; Communities; Cyanobacterium; DNA; Data Set; Detection; Diffusion; Disease; Escherichia coli; Eukaryota; Fluorescence; Goals; Health; Human; Image; Imaging Device; In Vitro; Maps; Measurement; Measures; Methods; Modeling; Molecular; Motion; Outcome; Phase; Physical condensation; Positioning Attribute; Prokaryotic Cells; Proteins; Resolution; Ribonucleoproteins; Role; Structure; System; Testing; Time; Tube; Work; cell fixing; cell type; commensal bacteria; data quality; fighting; human disease; improved; in vitro Model; innovation; microbial; molecular scale; nano; nanoscale; next generation; novel; novel strategies; organizational structure; scaffold; single molecule; spatiotemporal; statistics; superresolution imaging; superresolution microscopy; tool; ultra high resolution

Project Summary Molecular-scale interactions enable subcellular organization, but the current state-of-the-art does not include a generalizable method for measuring how molecules move and cooperate on the nanometer scale and in real time within the cell. This gap is particularly striking in bacteria cells. Accordingly, our picture of the organization of the bacterial cell is incomplete. This proposal aims to understand how cellular components organize—by scaffolding, aggregation, phase separation, or otherwise—to produce a general model of bacterial cell organization and ultimately enable us to promote commensal bacteria or fight human disease. Thus, we aim to measure the positioning, interactions, and motions of molecules in living bacterial cells in different protein systems implicated in the sub-cellular organization of these cells. This proposal will develop these next- generation super-resolution tools through three synergistic specific aims: (1) to super-resolve how single- molecule dynamics vary in space and in time in living bacterial cells; (2) to super-resolve sub-cellular interactions in space and time in living bacteria cells; and (3) to improve the detection of single molecules in living bacteria cells. The toolkit that we develop to map molecular motions and interactions will be broadly applicable to the single-molecule bacteriology community. Furthermore, by focusing on applications in bacterial cell biology, the tools developed in this project will have a widespread, positive biomedical impact by making accessible long- term, significant questions in microbial biology.

项目摘要 分子尺度的相互作用使亚细胞组织成为可能，但目前的最新技术水平不包括一个 一种测量分子在纳米尺度和真实的中如何运动和协作的通用方法 在细胞内的时间。这种差距在细菌细胞中尤其明显。因此，我们对该组织的看法 是不完整的。该提案旨在了解细胞成分如何组织 支架、聚集、相分离或其他方式-以产生细菌细胞的一般模型 组织，并最终使我们能够促进肠道细菌或对抗人类疾病。因此，我们的目标是 测量不同蛋白质中活细菌细胞中分子的定位、相互作用和运动 这些细胞的亚细胞组织所涉及的系统。本提案将在今后发展这些- 通过三个协同的具体目标生成超分辨率工具：（1）超分辨率如何单- 在活的细菌细胞中，分子动力学在空间和时间上变化;（2）超分辨亚细胞相互作用 在活细菌细胞中的空间和时间上;以及（3）改进活细菌中的单分子的检测 细胞我们开发的绘制分子运动和相互作用的工具包将广泛适用于 单分子细菌学社区。此外，通过关注细菌细胞生物学的应用， 在这个项目中开发的工具将产生广泛的，积极的生物医学影响，使长期的， 术语，微生物生物学中的重要问题。