CAREER: Exploring the 3D structure organization of genomes

University Of Southern California, Los Angeles CA

Investigators

Abstract

This award is made to the University of Southern California to develop methods for studying the 3D spatial organization of genomes. Knowing 3D genome structures and the spatial distributions of individual genes for various cell states would drastically change our view of the genome landscape. However, the 3D structures of genomes have yet to be determined. With the rapid accumulation of diverse genomic, epigenomic, and imaging data, the time has come to tackle this challenge by combining all available sources of information. This career-development plan proposes novel approaches to model the 3D structures of genomes by combining various large-scale data sources, by identifying important functional units in the 3D structures, and by characterizing structural elements in genome architectures through image analysis. The modeling of the higher-order genome structures will provide deep insights into gene regulation, and establish the missing link between genomics, functional genomics and structural biology. The 3D genome structure is highly variable, even among cells from an isogenic sample and no single structure can accurately describe all spatial properties of the genome. To address this challenge, this research will provide a novel population-based structural modeling approach, which constructs a population of 3D genome structures that are altogether entirely consistent with all available experimental data, including data from imaging and chromosome conformation capture experiments. This research will also provide novel tools for establishing links between spatial and functional organizations of genomes and will provide the atlases of functional spatial units in various genomes under different conditions. Finally this research will develop novel methods for pattern recognition in imaging of nuclei. A significant amount of effort is devoted to developing software and a web database for integrative 3D genome modeling (project URL: http://www.cmb.usc.edu/people/alber/3D-genome.html). This project has a strong commitment to directly involve students at all levels by building a strong training program in computational structural biology at USC. This research will be incorporated into an undergraduate course in structural bioinformatics as well as training of graduate students and post-doc fellows. Discussion forums will be held for minority high school and undergraduate students encouraging their pursuing higher education.