Statistical Physics of the Functional Organization of Chromosomes

染色体功能组织的统计物理学

• 批准号: 1206146
• 负责人: Jane Kondev
• 金额: $ 48万
• 依托单位: Brandeis University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-15 至 2016-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1206146&HistoricalAwards=false
• 关键词: Statistical; Physics; Functional; Organization; Chromosomes

TECHNICAL SUMMARYThis award supports theoretical research at the interface of physics and biology. The goal is to develop statistical physics models of chromosomes in cells that connect their structure to their function. In biology chromosomes are typically described as carriers of genetic information. They are also multi-component and dynamic polymer-like structures made of DNA and proteins that exhibits elements of both regularity and randomness. At the micron scale genes on chromosomes are often localized to particular regions of the cell, within which they undergo diffusive motion. This spatial and temporal organization of chromosomes has been quantitatively characterized using cell biology techniques but the rules that connect these physical properties to their function are largely unknown. The goal of this proposal is to develop coarse grained models based on ideas from statistical physics, which will elucidate the physical mechanisms that link chromosome structure at the micron scale to its function. Two fundamental biological processes will be considered: transcription and DNA recombination. The key question that will be addressed is how these processes are modulated and controlled by the spatial and temporal organization of genomes in cells. One of the key features of the theoretical research supported by this award is a close collaboration with experimental labs that study transcription and recombination quantitatively at the single molecule and single cell level. Theoretical predictions based on specific physical mechanisms of transcription and recombination will be tested in these labs. This award will support graduate students working at the interface of physics and biology. Physics graduate students engaged in research supported by this award will closely collaborate with biology students in collaborating labs. This mode of graduate training will promote an interdisciplinary research environment that will result in the cross-fertilization of ideas between statistical physics and molecular and cell biology. It will provide physics students with a unique opportunity to learn from students in life-science fields and help train them for research in interdisciplinary teams, which are being deployed with increasing frequency in industry and academia to tackle the outstanding challenges in biology and medicine.NON-TECHNICAL SUMMARYChromosomes are biological structures that perform functions that are essential to life, such as replication of DNA, the repair of damaged DNA, and the synthesis of new proteins. Chromosomes are also large molecular structures consisting of DNA and proteins whose shape and motion within the cell can be described in quantitative details using ideas from physics. The research supported by this award will provide the link between the biological functions of chromosomes and their physical attributes. In particular, it will lead to mathematical descriptions of how the nature of the dynamic and folded state of chromosomes within cells specifies their biological function. A mathematical description will be developed for the search process by which two genes on the same chromosome find each other within the crowded environment of the cell so as to enable the exchange of genetic material that occurs in the process of DNA recombination. Also, there is an abundance of experimental evidence that the folded state of DNA can interfere with the reading of genes in the process of transcription that leads up to protein synthesis, and the proposed research will formulate quantitative models of this unusual structure-function relation. The outcome of these theoretical investigations will be concrete proposals for quantitative experiments on DNA and chromosomes which will be carried out in collaborating biology laboratories that study DNA recombination and transcription. The combined theoretical and experimental approaches will lead to a precise quantitative description of chromosome structure and function. This award will support graduate students working at the interface of physics and biology. Physics graduate students engaged in theoretical research supported by this award will closely collaborate with biology students. These activities will promote an interdisciplinary research environment that will result in the cross-fertilization of ideas between statistical physics and molecular and cell biology. This environment will also provide the students with a unique opportunity to learn from students in biological fields and help train them for research in interdisciplinary teams which are being deployed with increasing regularity in industry and academia to tackle the outstanding challenges in biology and medicine.

该奖项支持物理学和生物学接口的理论研究。目标是开发细胞中染色体的统计物理模型，将其结构与功能联系起来。在生物学中，染色体通常被描述为遗传信息的载体。它们也是由DNA和蛋白质组成的多组分和动态聚合物样结构，具有规则性和随机性。在微米尺度上，染色体上的基因通常定位于细胞的特定区域，在该区域内它们经历扩散运动。染色体的这种时空组织已经用细胞生物学技术进行了定量表征，但是将这些物理性质与它们的功能联系起来的规则在很大程度上是未知的。该提案的目标是基于统计物理学的思想开发粗粒度模型，这将阐明将微米尺度的染色体结构与其功能联系起来的物理机制。两个基本的生物过程将被考虑：转录和DNA重组。将要解决的关键问题是这些过程是如何通过细胞中基因组的空间和时间组织来调节和控制的。该奖项支持的理论研究的关键特征之一是与实验室密切合作，在单分子和单细胞水平上定量研究转录和重组。基于转录和重组的特定物理机制的理论预测将在这些实验室进行测试。 该奖项将支持研究生在物理学和生物学的接口工作。从事该奖项支持的研究的物理学研究生将与生物学学生在合作实验室中密切合作。这种研究生培养模式将促进跨学科的研究环境，这将导致统计物理学与分子和细胞生物学之间的思想交叉。它将为物理学生提供一个独特的机会，向生命科学领域的学生学习，并帮助培训他们在跨学科团队中进行研究，这些团队在工业界和学术界越来越频繁地部署，以应对生物学和医学领域的突出挑战。非技术摘要染色体是生物结构，执行生命所必需的功能，如DNA的复制，修复受损的DNA和合成新的蛋白质。染色体也是由DNA和蛋白质组成的大分子结构，其在细胞内的形状和运动可以用物理学的思想定量描述。该奖项支持的研究将提供染色体的生物学功能与其物理属性之间的联系。特别是，它将导致细胞内染色体的动态和折叠状态的性质如何指定其生物学功能的数学描述。将为搜索过程开发一个数学描述，通过该搜索过程，同一染色体上的两个基因在细胞的拥挤环境中找到彼此，以便能够在DNA重组过程中发生遗传物质的交换。此外，有大量的实验证据表明，DNA的折叠状态可以干扰导致蛋白质合成的转录过程中基因的阅读，拟议的研究将制定这种不寻常的结构-功能关系的定量模型。这些理论研究的结果将是DNA和染色体定量实验的具体建议，这些实验将在研究DNA重组和转录的合作生物实验室中进行。理论和实验相结合的方法将导致染色体结构和功能的精确定量描述。该奖项将支持研究生在物理学和生物学的接口工作。从事该奖项支持的理论研究的物理学研究生将与生物学学生密切合作。这些活动将促进一个跨学科的研究环境，这将导致统计物理学与分子和细胞生物学之间的思想交叉。这种环境还将为学生提供一个独特的机会，向生物学领域的学生学习，并帮助培养他们在跨学科团队中进行研究，这些团队在工业和学术界越来越经常地部署，以应对生物学和医学方面的突出挑战。