CAREER: Imaging enhancer-mediated transcriptional regulation in 3D genome

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This project will elucidate the role of 3D genome organization in gene regulation during development by engaging graduate, undergraduate, and high school students in the cutting-edge field of quantitative biology. Proper gene regulation is crucial for the smooth execution of various cellular functions. Indeed, too much or too little gene expression in the wrong place or at the wrong developmental stages often leads to developmental defects. The folded structure of the DNA polymer plays an important role in gene regulation, in addition to direct interactions between regulatory elements and the target gene. The overall goal of the project is to characterize the spatial and temporal range of gene expression that ensures normal development upon perturbation of 3D genome organization in early Drosophila embryos. An undergraduate design project in quantitative biology and a virtual outreach program for high school students will be established to enhance students’ involvement in interdisciplinary research in quantitative biology. The recent development of various “seq” techniques have advanced the field of transcriptional regulation by providing a genome-wide perspective of enhancer-promoter interactions and gene activity. However, it is still unclear how long or how closely a specific arrangement of architecture proteins, enhancers, and promoters in a given cell should be maintained to result in proper gene expression. This question will be addressed by tracking dynamic changes in chromatin organization and transcriptional activity in individual living cells. Multiple approaches, including genome editing, quantitative live imaging and mathematical modeling will be employed in early Drosophila embryos to examine the structure-function relationships of genome topology and gene activity. Specifically, long-range enhancer-promoter interactions and inter-allelic associations will be perturbed and the effects on transcriptional dynamics will be characterized in this project.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.