URoL: Epigenetics 1: Genomic and epigenetic determinants of nuclear morphology and mechanics

URoL：表观遗传学 1：核形态和力学的基因组和表观遗传决定因素

• 批准号: 2022048
• 负责人: Eric Richards
• 金额: $ 50万
• 依托单位: Boyce Thompson Institute Plant Research
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2022048&HistoricalAwards=false
• 关键词: URoL; Epigenetics; Genomic; epigenetic; determinants

In biology, as in architecture, form defines function. Biological organisms are built to tolerate environmental stressors in much the same way as skyscrapers are built to withstand forces of wind and gravity. This project focuses on understanding the relationship between form and function in the nucleus, the cellular compartment that houses and organizes the hereditary material in the form of highly-compacted molecules of DNA. The key question to be addressed is, how are nuclear form and function influenced by mechanical properties? Experiments will apply mechanical forces to individual animal and plant cells, and changes in the shape of the nuclei and the function of the enclosed DNA will be measured. The results are expected to improve our ability to predict and manipulate how organisms respond and adapt to mechanical stresses encountered in the environment. In addition to the scientific advances, the project will have educational impact by providing training for early-career scientists to learn and implement principles and techniques that bridge biology and engineering.This research combines comparative and experimental approaches to define rules that specify the physical and morphological characteristics of nuclei in both the animal and plant kingdoms. Key to these studies is the ability to measure the physical properties of individual nuclei through bioengineering and biophysical approaches, using microscopic examination of isolated organelles and cells as they transit through spatial constrictions in microfluidic devices. The experimental plan seeks to understand the interplay of epigenetically-relevant features--such as chromatin modifications—with nuclear structure and mechanics to uncover the role that the environment plays in modulating these interactions. Elucidating the mechanisms mediating such interactions will bring us closer to an understanding of how the environment influences (epi)genome function and, ultimately, plant and animal traits.This project is funded by the Understanding the Rules of Life: Epigenetics Program, administered as part of NSF's Ten Big Ideas through the Division of Emerging Frontiers in the Directorate for Biological Sciences. Co-funding is provided by the Cellular Dynamics and Function Program, Division of Molecular and Cellular Biosciences, Directorate for Biological Sciences.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.

在生物学中，如在体系结构中，形式定义了功能。生物生物的建造是为了耐受环境压力的方式，与摩天大楼的建造方式几乎相同。该项目的重点是理解核中形式和功能之间的关系，核的形式和功能是以高度压缩的DNA分子的形式容纳和组织遗传物质的细胞室。要解决的关键问题是，核形式和功能如何受到机械性能的影响？实验将向单个动物和植物细胞应用机械力，并将测量核的形状变化，并测量封闭的DNA的功能。预计结果将提高我们预测和操纵生物如何反应和适应环境中遇到的机械压力的能力。除科​​学进步外，该项目还将通过为早期职业科学家提供培训来学习和实施桥接生物学和工程学的原理和技术，从而产生教育影响。这项研究结合了定义规则的比较和实验方法，以指定动物和植物王国中核的物理和形态特征的规则。这些研究的关键是通过微观细胞器和细胞通过微流体设备中的空间约束来测量生物工程和生物物理方法通过生物工程和生物物理方法测量物理性质的能力。该实验计划旨在了解与表观遗传相关的特征（例如染色质修饰）的相互作用，并具有核结构和机制，以揭示环境在调节这些相互作用中所扮演的作用。阐明介导这种相互作用的机制将使我们更加了解环境如何影响（EPI）基因组功能以及最终是动植物特征。该项目由理解生活规则：表观遗传学计划的理解资助，通过NSF的十个重大思想，是通过在生物学上涉及生物学局长的十个大想法的一部分。共同基金会由蜂窝动力学和功能计划，分子和细胞生物科学的划分，生物科学局提供。该奖项反映了NSF的法定任务，并且我们是否使用基金会的智力优点和更广泛的影响标准通过评估我们被评估诚实地诚实地支持。

项目成果

The edge of the nucleus: Variations on a theme

• DOI: 10.1016/j.devcel.2021.12.013
• 发表时间: 2022-01-10
• 期刊: DEVELOPMENTAL CELL
• 影响因子: 11.8
• 作者: Choi, Junsik;Richards, Eric J.
• 通讯作者: Richards, Eric J.

Mechanobiology of the cell nucleus

• DOI: 10.1063/5.0135299
• 发表时间: 2022-12-01
• 期刊: APL BIOENGINEERING
• 影响因子: 6
• 作者: Lammerding，Jan;Engler，Adam J. J.;Kamm，Roger
• 通讯作者: Kamm，Roger

Seminars in cell and development biology on histone variants remodelers of H2A variants associated with heterochromatin

• DOI: 10.1016/j.semcdb.2022.02.026
• 发表时间: 2022-11-20
• 期刊: SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
• 影响因子: 7.3
• 作者: Berger，Frederic;Muegge，Kathrin;Richards，Eric J.
• 通讯作者: Richards，Eric J.