CAREER: Organization and Force Production in Bacteria

职业：细菌的组织和强制生产

• 批准号: 0844466
• 负责人: Joshua Shaevitz
• 金额: $ 94.33万
• 依托单位: Princeton University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0844466&HistoricalAwards=false
• 关键词: CAREER; Organization; Force; Production; Bacteria

In this CAREER proposal the PI proposes to study a fundamental question in biology: How do nanometer-scale proteins give rise to micron-scale forces at the cellular level? Specifically, the PI will determine the mechanisms of chromosome segregation and cell division in bacteria. The proposed experiments will investigate intracellular organization and force generation in bacteria through (i) imaging, (ii) mechanical perturbation and (iii) force measurement. Super-resolution, three-dimensional imaging will be used to quantify the geometric conformations of cytoskeletal proteins inside cells and how they respond to externally applied forces. The three-dimensional trajectories of actively segregated regions of DNA will be revealed using single particle tracking. In addition, the role of local cell curvature in the placement of the cell division plane and the ability of the contractile ring to generate mechanical force during cell division will be probed with atomic force microscopy. The proposed education plan provides learning opportunities for future biophysical scientists through combined (i) course development, (ii) hands-on observations and (iii) a multimedia cellular environment. The PI will develop and teach two new courses on Biological Physics that integrate research results in a broader biophysical context through his joint appointment in the Department of Physics and the Lewis-Sigler Institute for Integrative Genomics at Princeton University. To motivate the next generation of scientists, the PI will work with local middle school students as part of Princeton Universitys Science and Engineering Expo, introducing them firsthand to the physics of cellular locomotion through microscopy and modeling activities. An interactive software program, partly based on imaging data from this proposal, will be created that allows students to explore the crowded and fascinating three-dimensional world that exists inside cells.The long term goal of the proposal is to develop novel methods for studying single molecule dynamics in living systems and to understand how different length and time scales are integrated for a living bacteria or cell to emerge. This project encompasses aspects of cell biology, molecular biophysics, physics, and computational biology. The students working on the project will be trained at the interface of several fields of science. The proposed research has all ingredients to be truly transformational. This project is jointly supported by the Physics of Living Systems Program Molecular in the Division of Physics at the Physical Sciences Directorate and by the the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences.

在这个职业计划中，PI建议研究生物学中的一个基本问题：纳米级蛋白质如何在细胞水平上产生微米级的力？具体而言，PI将确定细菌中染色体分离和细胞分裂的机制。拟议的实验将通过（i）成像，（ii）机械扰动和（iii）力测量来研究细菌中的细胞内组织和力产生。超分辨率三维成像将用于量化细胞内细胞骨架蛋白的几何构象以及它们如何对外部施加的力作出反应。使用单粒子跟踪将揭示DNA活跃分离区域的三维轨迹。此外，局部细胞曲率的细胞分裂平面的位置和收缩环的能力，在细胞分裂过程中产生的机械力的作用将探测与原子力显微镜。拟议的教育计划通过综合（一）课程开发、（二）实践观察和（三）多媒体细胞环境，为未来的生物物理科学家提供学习机会。PI将开发和教授两门新的生物物理课程，通过他在普林斯顿大学物理系和Lewis-Sigler综合基因组学研究所的联合任命，将研究成果整合到更广泛的生物物理背景下。为了激励下一代科学家，PI将与当地中学生合作，作为普林斯顿大学科学与工程博览会的一部分，通过显微镜和建模活动向他们介绍细胞运动的物理学。该项目的长期目标是开发新的方法来研究生命系统中的单分子动力学，并了解不同的长度和时间尺度是如何整合成一个活的细菌或细胞的。该项目包括细胞生物学，分子生物物理学，物理学和计算生物学方面。从事该项目的学生将接受多个科学领域的培训。拟议中的研究具有真正变革性的所有要素。该项目由物理科学理事会物理学部的生命系统物理学计划分子和生物科学理事会的分子和细胞生物科学部共同支持。