Research Summary

Protein-protein interactions of chromatin bound proteins in shaping the genome architecture

How different cell types acquire and maintain their identity is a fundamental problem in biology. Cellular identity is determined by the combinatorial expression state of hundreds of genes, which in turn is regulated by three-dimensional (3D) organization of chromatin. Multiscale organization of chromatin ranging from loops between enhancers and promoters (1-1000s kb), formation of Topologically-Associating-Domains (TADs) by contiguous sequences (10s-1000s kb) to segregation of chromosomes into territories, and trans-interactions between domains on different chromosomes has been linked with development, differentiation and disease. Although application of various biochemical, genome sequencing, imaging and polymer modeling methods have significantly improved our understanding of genome organization, the principles governing the three-dimensional organization of genome are just beginning to get uncovered. We are interested in understanding the mechanical basis of genome organization. To address this problem we are using an interdisciplinary approach including protein biochemistry/biophysics, genome wide sequencing based methods (like ChIP-seq, Chromosome conformation capture, MNase-seq and RNA-seq), mass spectrometry to polymer modeling.