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

在生物学中，就像在建筑学中一样，形式决定了功能。生物有机体的建造是为了承受环境压力，就像摩天大楼的建造是为了承受风和重力一样。这个项目的重点是理解细胞核中形式和功能之间的关系，细胞核是细胞隔间，以高度紧密的DNA分子的形式容纳和组织遗传物质。要解决的关键问题是，核的形式和功能是如何受到机械性能的影响的？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。该结果有望提高我们预测和操纵生物体如何应对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应用连接生物学和工程学的原理和技术，从而产生教育影响。这项研究结合了比较和实验的方法来定义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，因为它们在微流体装置的空间收缩中传输。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。该项目由理解生命规则：表观遗传学项目资助，该项目由生物科学理事会新兴前沿部门管理，是NSF十大理念的一部分。联合资助由生物科学理事会分子和细胞生物科学部细胞动力学和功能项目提供。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.