CAREER: Direct Measurement of Intranuclear Strain and Gene Expression in Single Cells in Vivo

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This project will significantly advance the understanding of the physical regulation of the cell nucleus in structurally complex and hierarchical biological tissues. The nucleus is a central membrane-bound organelle in the cell that functions to control fundamental cellular activities that are critical to normal physiology. More broadly, the research activities may impact tissue engineering, regenerative medicine, and related fields, by establishing the ability to study mechanisms of nuclear strain and gene expression in single cells, including studies of rare cell populations within tissues and biomaterials. The education plan is designed to provide an interactive and problem-solving approach toward learning. The education activities emphasize undergraduate and graduate course development in mechanobiology, and broaden a partnership between the awardee's institution and a children's museum to promote learning in science and engineering from an early age.The research objective of this Faculty Early Career Development (CAREER) award is to apply advanced microscopy, image registration, and molecular biology methods to study the biomechanics of the cell nucleus and basic mechanisms that determine the physical regulation of gene expression. Studies conducted under this award will image the nucleus of single cells embedded in native tissue that is perturbed by mechanical force, and determine the influence of cytoskeleton proteins on intranuclear shape, deformation, and activity. A multiscale and translational approach will also study the nucleus in normal and genetically modified mice to investigate how mechanical force regulates gene expression in vivo. The knowledge gained from the research activities will reveal how subcellular strain is altered in disease and injury, and studies will establish new analysis tools for the noninvasive, in vivo, and functional biomechanical assessment of nuclei in model systems.