CAREER: Mechanobiology of the Chromatin Remodeling: Implications in Gene Expression, Physiology, and Pathology

职业：染色质重塑的力学生物学：对基因表达、生理学和病理学的影响

• 批准号: 2236710
• 负责人: Soham Ghosh
• 金额: $ 59.86万
• 依托单位: Colorado State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2236710&HistoricalAwards=false
• 关键词: CAREER; Mechanobiology; Chromatin; Remodeling; Implications

This Faculty Early Career Development (CAREER) grant supports research focused on discovering a fundamental mechanism inside the cell nucleus that may dramatically improve our understanding of how several degenerative diseases associated with fibrosis occur and progress. Many pathological conditions inside the human body are associated with an abnormal mechanical environment in the tissues. Optimal mechanical force is required inside tissues to keep the cells functional and healthy. This project will elucidate how the biological system's healthy or pathological mechanical environment affects the structure and function of cells and tissues through chromatin remodeling – a novel epigenetic determinant of gene expression inside the cell nucleus. This knowledge can potentially provide new therapeutic strategies to treat a myriad of degenerative diseases, such as fibrosis in the lungs, heart, kidney, liver, skin, and blood vessels. The proposed research will be complemented by establishing a comprehensive educational and outreach program based on curriculum enrichment, quantitative biology training, and disseminating biomechanics knowledge in K-12 and students underrepresented in STEM.This project aims to discover how the tensile force at the tissue level reaches the intranuclear space to remodel the chromatin and determine the gene expression. The researchers will utilize high-resolution single cell microscopy, knowledge of mechanics, and advanced image analysis techniques to answer several outstanding questions in mechanobiology. The work will address: 1) how mechanical forces drive chromatin remodeling and gene expression; 2) how the changes in chromatin remodeling and gene expression affect the cell and tissue mechanical properties that determine the tissue phenotype; and 3) how to intervene in the mechano-epigenetic pathway to restore normalcy in degenerated cells or tissues. This project will allow the PI to advance the boundaries of the existing knowledge in chromatin mechanobiology, epigenetics, and gene expression mechanisms and establish a long-term career in mechanobiology to solve various problems in life sciences and medicine.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.

这项教师的早期职业发展（职业）赠款支持研究的研究，旨在发现细胞核心内部的基本机制，这可能会大大提高我们对与纤维化相关的几种退化性疾病的理解。人体内部的许多病理状况与组织中的机械环境异常有关。需要最佳的机械力在组织内部保持细胞功能和健康。该项目将阐明生物系统的健康或病理机械环境如何通过染色质重塑（一种新型的表观遗传学决定因素）在细胞核心内的新表观遗传决定因素。这些知识可能会提供新的治疗策略来治疗多种退行性疾病，例如肺，心脏，肾脏，肝脏，皮肤和血管中的纤维化。拟议的研究将通过建立基于课程丰富，定量生物学培训并传播K-12中的生物力学知识的全面教育和外展计划，并且在STEM中代表性不足的学生旨在发现组织水平的拉伸力量如何使其表达型chratemel和Charmatin ne Genematile semples。研究人员将利用高分辨率的单细胞显微镜，力学知识和高级图像分析技术来回答机械生物学中的几个出色问题。工作将解决：1）机械力如何驱动染色质重塑和基因表达； 2）染色质重塑和基因表达的变化如何影响决定组织表型的细胞和组织机械性能； 3）如何干预机械性景观途径以恢复退化的细胞或时间因素。该项目将使PI能够在染色质机制，表观遗传学和基因表达机制方面提高现有知识的界限，并在机制中建立长期职业，以解决生命科学和医学中的各种问题。该奖项反映了NSF的法定任务，并认为通过基金会的知识优点和广泛的criperia criperia criperia criperia criperia criperia criperia criperia criperia rection the priews this奖。