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: 10341319
• 负责人: Julie Biteen
• 金额: $ 31.73万
• 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/10341319
• 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; Microscopy; Modeling; Molecular; Motion; Outcome; Phase; Physical condensation; Positioning Attribute; Prokaryotic Cells; Proteins; Resolution; Ribonucleoproteins; Role; Rotation; Structure; System; Testing; Time; Tube; Work; cell type; commensal bacteria; data quality; density; fighting; human disease; improved; in vitro Model; innovation; microbial; molecular scale; nanoscale; next generation; novel; novel strategies; organizational structure; scaffold; single molecule; spatiotemporal; statistics; tool

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 分子尺度相互作用可以实现亚细胞组织，但当前的最新组织不包括 可概括的方法，用于测量分子如何在纳米尺度上移动和坐标 在单元格内的时间。在细菌细胞中，该差距特别明显。根据我们对组织的照片 细菌细胞的不完整。该建议旨在了解细胞组件如何组织 脚手架，聚集，相位分离或其他方式产生细菌细胞的通用模型 组织并最终使我们能够促进共生细菌或与人类疾病作斗争。那我们的目标是 测量不同蛋白质活细胞中分子的定位，相互作用和运动 这些细胞的细胞组织中实现的系统。该提案将发展这些下一步 通过三个协同特定目的的生成超分辨率工具：（1）超级解决单一 分子动力学在活细胞细胞中的空间和时间变化； （2）超溶解亚细胞相互作用 在活细胞细胞中的空间和时间中； （3）改善活细菌中单分子的检测 细胞。我们开发以绘制分子运动和相互作用的工具包将广泛适用于 单分子细菌群落。此外，通过关注细菌细胞生物学的应用， 该项目中开发的工具将通过使可访问的长期可访问，从而产生宽大的积极生物医学影响 术语，微生物生物学中的重要问题。