NSF-ANR: Physics of chromosomes through mechanical perturbations

NSF-ANR：通过机械扰动研究染色体物理学

• 批准号: 2210558
• 负责人: Leonid Mirny
• 金额: $ 57.8万
• 依托单位: Massachusetts Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2210558&HistoricalAwards=false
• 关键词: NSF; ANR; Physics; chromosomes; through

DNA molecules are not only carriers of genetic information but are also exceedingly long polymers. These polymers (chromosomes) are fascinating physical systems with quenched disorder, complex topological properties, and driven far from equilibrium by active processes. In this project the investigators will examine the Physics of Chromosomes by integrating approaches of theoretical and experimental biophysics of two leading groups with complementary expertise in Physics of Living Systems. The Coulon lab, at CNRS Paris, has pioneered the use of mechanical perturbation of chromosomes by moving a genomic locus within a living cell by external magnetic field. Such perturbations are methodologically novel and can provide unique information about the physical state and dynamics of chromosomes. Gaining insights from these measurements requires development of physical models of chromosome organization. The Mirny lab, at MIT, has been developing polymer models of chromosomes aiming to understand principles and mechanisms underlying chromosomes folding. The Coulon and the Mirny labs have been collaborating on this project and have published the first paper that provides extensive Preliminary Data in support of this project. Current understanding of chromosome organization is largely based on data obtained through non-perturbative experiments. The ability to apply forces and mechanically manipulate chromosomal loci in a living cell provide a unique handle to answer long standing –but yet unanswered– questions: i) What is the physical nature of chromatin? ii) How strong are molecular forces in the chromatin? iii) What mechanism underlies maintenance of chromosomal territories? This theory-driven mechanical probing of chromosomes will allow understanding of the material nature of chromosomes and uncovering new physical mechanisms underlying chromosome organization and dynamics. This project will pursue outreach activities that include Public lectures in Boston and région Île-de-France given jointly by Mirny and Coulon; development of a children's book on physics of chromosomes and the nucleus, jointly with Actin Art association and the ‘Esprits Curieux’ initiative of the Institut Curie; and the involvement of high school students in research through MIT PRIMES program.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

DNA 分子不仅是遗传信息的载体，而且是超长的聚合物，这些聚合物（染色体）是令人着迷的物理系统，具有猝灭的无序性、复杂的拓扑特性，并且在活跃过程中远离平衡。巴黎 CNRS 的 Coulon 实验室将两个领先小组的理论和实验生物物理学方法与生命系统物理学的互补专业知识相结合，率先利用染色体的机械扰动进行染色体物理学研究。通过外部磁场移动活细胞内的基因组位点在方法上是新颖的，并且可以提供有关染色体物理状态和动态的独特信息，需要开发染色体组织的物理模型。麻省理工学院的 Coulon 和 Mirny 实验室一直在开发染色体聚合物模型，旨在了解染色体折叠的原理和机制，并发表了第一篇论文，提供了支持该项目的广泛初步数据。目前对染色体组织的理解主要基于通过非微扰实验获得的数据，在活细胞中施加力和机械操纵染色体位点的能力为回答长期存在但尚未解答的问题提供了独特的方法：获得i)。染色质的物理性质是什么？ ii) 染色质中的分子力有多强？ iii) 这种由理论驱动的染色体机械探测将有助于理解染色体的结构。该项目将开展外展活动，包括由 Mirny 和 Coulon 联合在波士顿和法兰西岛地区举办的公开讲座，并编写一本关于染色体物理学的儿童读物；和 nucleus 与 Actin 艺术协会和居里研究所的“Esprits Curieux”倡议以及高中生通过麻省理工学院 PRIMES 项目参与研究。该奖项反映了通过使用基金会的智力价值和更广泛的影响审查标准进行评估，NSF 的法定使命被认为值得支持。