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，就像在建筑学中一样，形式决定了功能。生物有机体是为了承受环境压力而建造的，就像摩天大楼是为了承受风力和重力一样。该项目的重点是了解细胞核中形式和功能之间的关系，细胞核是以高度紧凑的DNA分子形式容纳和组织遗传物质的细胞室。要解决的关键问题是，核的形式和功能如何受到机械性能的影响？ 实验将对单个动物和植物细胞施加机械力，并测量细胞核形状和封闭DNA功能的变化。 这些结果有望提高我们预测和操纵生物体如何响应和适应环境中遇到的机械应力的能力。 除了科学进步之外，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连接生物学和工程学的原理和技术，从而产生教育影响。该研究结合了比较和实验方法，以确定动物和植物王国中细胞核的物理和形态特征的规则。这些研究的关键是通过生物工程和生物物理方法测量单个细胞核的物理特性的能力，使用显微镜检查分离的细胞器和细胞，因为它们通过微流体装置中的空间收缩。该实验计划旨在了解表观遗传相关特征（如染色质修饰）与核结构和力学的相互作用，以揭示环境在调节这些相互作用中所起的作用。阐明介导这种相互作用的机制将使我们更接近于了解环境如何影响（epi）基因组功能，并最终影响植物和动物的性状。该项目由理解生命的规则：表观遗传学计划资助，作为NSF十大理念的一部分，通过生物科学理事会新兴前沿部门进行管理。 共同资助是由细胞动力学和功能计划，分子和细胞生物科学部，生物科学理事会。这个奖项反映了NSF的法定使命，并已被认为是值得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的支持。