Biomechanical Regulation of Intranuclear Elastography and Gene Location in Single Cells

单细胞核内弹性成像和基因定位的生物力学调节

• 批准号: 2212121
• 负责人: Corey Neu
• 金额: $ 46.23万
• 依托单位: University of Colorado at Boulder
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2212121&HistoricalAwards=false
• 关键词: Biomechanical; Regulation; Intranuclear; Elastography; Gene

This grant will support research about how the cells of our bodies react to mechanical forces. The results of this work will greatly advance progress in science and improvements in national health. Mechanobiology is a science that seeks to explain how cells actively adapt to mechanical forces. Understanding the mechanobiology of cells can lead to new therapies to treat damage due to aging and disease. There are many ways that cells react to force, which often involves the cell nucleus that contains the DNA defining our genetic code. However, we do not yet know how mechanical force stimulates the cell to alter its structure and position of DNA. This award supports fundamental research to measure gene expression in the cell nucleus and how it changes with applied forces. This will reveal mechanisms that cells use to alter their biological function triggered by force. Understanding this complex biological process may lead to new therapeutic and diagnostic approaches in medical science. This research project is multidisciplinary, and impacts the sciences of biomedical engineering, imaging, biomechanics, cell biology, and materials science. This project will also target broad participation of underrepresented groups in research, including children. This outreach is anticipated to positively impact education in science and engineering.The objective of this project is to study the structural and biomechanical regulation of nuclear gene expression using new methods to measure elastography and gene positioning in living cells. Structural complexity and hierarchy are hallmarks of the cell nucleus, and the expression patterns of protein-coding genes in the nucleus are regulated by multiple factors, including the dynamics of chromatin organization and movement. Unfortunately, how intranuclear biomechanics and gene position relate to complex processes like transcription are still not well defined. Our work aims to provide new methods and knowledge to biomechanics and mechanobiology communities, including first-of-its-kind methods and data describing spatial patterns of strain and material properties for nuclei of single cells challenged by physiologically-relevant conditions, direct evidence relating gene activation to gene location and chromatin mechanics following cell stimuli, and platform technologies to more broadly explore mechanisms of mechanobiology in the nucleus.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.

这项拨款将支持关于我们身体细胞如何对机械力作出反应的研究。 这项工作的结果将大大推动科学进步和国民健康的改善。机械生物学是一门试图解释细胞如何主动适应机械力的科学。 了解细胞的机械生物学可以导致新的疗法来治疗衰老和疾病造成的损伤。细胞对力的反应有很多种方式，其中通常涉及包含定义我们遗传密码的DNA的细胞核。然而，我们还不知道机械力如何刺激细胞改变其结构和DNA的位置。 该奖项支持基础研究，以测量细胞核中的基因表达以及它如何随着外力而变化。 这将揭示细胞用来改变其生物功能的机制。了解这一复杂的生物过程可能会导致医学科学中新的治疗和诊断方法。该研究项目是多学科的，并影响生物医学工程，成像，生物力学，细胞生物学和材料科学的科学。这一项目还将以包括儿童在内的代表性不足的群体广泛参与研究为目标。 该项目的目的是利用新方法测量活细胞中的弹性成像和基因定位，研究核基因表达的结构和生物力学调节。结构复杂性和层次性是细胞核的标志，并且细胞核中蛋白质编码基因的表达模式受多种因素调节，包括染色质组织和运动的动力学。不幸的是，核内生物力学和基因位置如何与转录等复杂过程相关仍然没有很好的定义。我们的工作旨在为生物力学和机械生物学社区提供新的方法和知识，包括描述受生理相关条件挑战的单细胞核的应变和材料特性的空间模式的首创方法和数据，将基因激活与基因定位和细胞刺激后的染色质力学相关的直接证据，该奖项反映了NSF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。