CAREER: Dynamics of gene regulation

The way the DNA in the cells in our bodies is organized and interacts is essential for regulating gene expression. Proper gene regulation is required for the healthy functioning of cells, and impaired DNA organization and interactions have been implicated in many different diseases. Despite their importance, these processes are challenging to study at the required spatial and temporal resolution. This project aims to overcome these challenges by developing and applying advanced tools to directly visualize, quantify, and correlate DNA dynamics, organization, and gene activity in real-time with unprecedented resolution. Integrated with this research is a plan for educational and volunteer outreach activities targeting high school teachers and students from the Houston Independent School District. Together, these efforts will foster a synergistic program of research and educational enrichment that advances science and increases STEM opportunities for the next generation of scientists. This project will develop labeling and imaging tools and apply them to study the dynamics and interactions of key regulatory components of the genome, such as enhancers and promoters, and to correlate these interactions with gene expression in unperturbed human cells and during well-controlled perturbations of nuclear function. Using innovative labeling strategies for targeting specific genomic loci in the accessible genome, advanced 3D imaging at the nanoscale, and quantitative analysis of gene expression, this work will yield critical new insights into how the genomic structure, organization, and local epigenetic state regulate transcription. It will allow mapping of fundamental physical and molecular mechanisms underlying gene regulation, potentially revealing conserved predictive relationships. The methodologies developed in this project can be broadly employed to investigate the kinetics of interactions among various regulatory elements involved in chromatin reorganization and gene regulation, and they are generalizable for studies of a diverse range of biological systems and diseases in the future. 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.