Transitions: Mechanical Regulation of Transcription Factor Dynamics, Chromatin Accessibility and Gene Expression

转变：转录因子动力学、染色质可及性和基因表达的机械调节

• 批准号: 2132922
• 负责人: Arpita Upadhyaya
• 金额: $ 74.89万
• 依托单位: University of Maryland, College Park
• 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: 2022-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2132922&HistoricalAwards=false
• 关键词: Transitions; Mechanical; Regulation; Transcription; Factor

The regulation of gene expression by the mechanical microenvironment, which is essential for key biological processes such as development, wound healing, and immune function is poorly understood. In this project, the PI will obtain training and initiate a new line of research to study the regulation of transcription by the mechanical properties of the cellular microenvironment. The knowledge gained will help lead to an understanding of many aspects of cell and tissue function. The Broader Impacts of the work include the intrinsic merit of the research as cells encounter complex microenvironments with varied physical properties and disruption of their ability to sense these properties leads to pathologies such as cancer progression and metastasis. In addition, graduate students and undergraduates will be trained in interdisciplinary research. The PI will also work with programs at University of Maryland to host summer research programs for students from mid-Atlantic minority-serving institutions and provide graduate students with experience in mentoring a diverse group of students. This project will enable a shift in the research focus of the PI to a new area at the interface between physics and biology – how the mechanical microenvironment regulates transcription and gene expression. In the professional development portion of the project, the PI, and members of her lab, will learn and implement various techniques for monitoring transcriptional dynamics in living cells using single molecule imaging and molecular engineering of reporter systems. The PI and her lab members will also be trained in next generation sequencing techniques to assess genome wide changes induced by substrate mechanics. The long-term goal of this work is to apply these transformative experimental methods and predictive theories to provide insights into how the mechanical environment affects in gene expression dynamics.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.

机械微环境对基因表达的调控对于发育、伤口愈合和免疫功能等关键生物过程至关重要，但人们对其了解甚少。在这个项目中，PI将获得培训并启动一条新的研究路线，研究细胞微环境的机械特性对转录的调节。所获得的知识将有助于了解细胞和组织功能的许多方面。这项工作的广泛影响包括研究的内在价值，因为细胞遇到具有不同物理特性的复杂微环境，并且它们感知这些特性的能力被破坏会导致诸如癌症进展和转移等病理。此外，研究生和本科生将接受跨学科研究的培训。PI还将与马里兰大学（University of Maryland）的项目合作，为大西洋中部少数族裔院校的学生举办暑期研究项目，并为研究生提供指导不同学生群体的经验。该项目将使PI的研究重点转移到物理学和生物学之间的一个新领域-机械微环境如何调节转录和基因表达。在项目的专业发展部分，PI和她的实验室成员将学习并实施各种技术，利用单分子成像和报告系统的分子工程来监测活细胞中的转录动力学。PI和她的实验室成员还将接受下一代测序技术的培训，以评估由底物力学引起的基因组广泛变化。这项工作的长期目标是应用这些变革性的实验方法和预测理论，为机械环境如何影响基因表达动力学提供见解。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。

项目成果

Transcription Factor Dynamics: One Molecule at a Time

转录因子动力学：一次一个分子

• DOI: 10.1146/annurev-cellbio-022823-013847
• 发表时间: 2023
• 期刊: Annual Review of Cell and Developmental Biology
• 影响因子: 11.3
• 作者: Wagh, Kaustubh;Stavreva, Diana A.;Upadhyaya, Arpita;Hager, Gordon L.
• 通讯作者: Hager, Gordon L.