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

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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.