Biophysics of the bacterial nucleoid: Structure, replication, and segregation of the E. coli chromosome

该奖项是根据2009年美国复苏和再投资法案(公法111-5)资助的。在这个项目中，PI建议基于对原核细胞中大量荧光标记菌株的成像来测量、分析和建模染色体构象。PI还将引入用于轨迹位移技术的协方差矩阵，并使用它来表征和定量测量类核及其细胞系的结构和力学性质。此外，还将利用轨迹分布函数、协方差矩阵和基于时间推移的技术，通过定量描述和模拟突变体和药物对类核结构的影响来研究类核组织和分离的机制。研究生、访问学生和博士后与怀特黑德生物医学研究所的PI和布兰迪斯大学物理系的PI共同研究本提案中概述的问题，将在跨学科环境中工作，并将学习如何将细胞生物学和遗传学以及生物信息学技术与单分子、理论和计算生物物理学相结合。拟议的研究将与Brandeis大学生物物理专业本科课程的进一步发展和由共同PI发起的Brandeis研究生数量生物学课程以及编写教科书《细胞的物理生物学》第二版紧密结合在一起。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).In this project the PI proposes to measure, analyze, and model chromosome conformation based on the imaging of an extensive collection of fluorescently-labeled strains in prokaryotic cells. The PI will also introduce the co-variance matrix for loci displacement technique and use it to characterize and quantitatively measure the structural and mechanical properties of the nucleoid and its cellular tethering. The mechanism of nucleoid organization and segregation by quantitatively characterizing and modeling the effect of partitioning mutants and drugs on nucleoid structure using locus-distribution-function, covariance-matrix, and time-lapse-based techniques will be studied as well. Graduate students, visiting students, and postdocs working with the PI at the Whitehead Institute for Biomedical Research and the co-PI at the Department of Physics at Brandeis University on the problems outlined in this proposal will work in an interdisciplinary environment and will learn how to combine cell-biology and genetic, and bioinformatic techniques with single-molecule, theoretical and computational biophysics. The proposed research will be tightly coupled to the further development of courses for the undergraduate Biological Physics major and the graduate Quantitative Biology program at Brandeis, initiated by the co-PI, as well as working on the second edition of the textbook Physical Biology of the Cell.