DNA of the human genome is 2m long and is folded into chromosomes that fit in 10-micron cellular nucleus. How are these long polymers of DNA folded and organized in 3D inside the nucleus? How can proteins that are much smaller than chromosomes drive chromosome compaction, segregation or control functional interactions at much larger scales? Recently developed experimental technique (Hi-C) provides comprehensive information about frequencies of spatial interactions between genomic loci. Inferring principles of 3D organization of chromosomes from these data is a challenging biophysical problem, rooted in statistical physics of polymers. Our works suggest that chromosomes are organized by an active, energy-consuming, process of loop extrusion. We proposed that loop extrusion is a universal mechanism responsible for formation of domains in interphase [1,2], and chromosome compaction and segregation in metaphase .
Professor Mirny's research focuses on computational structural and system biology. His multidisciplinary approach combines first-principle physics with the analysis of biological systems such as genes, proteins, and metabolic pathways. His efforts in computational structural biology involve the development of novel computational tools to analyze and predict structures of proteins, their complexes, and protein-DNA interactions. In these studies, Prof. Mirny seeks to identify amino acids that determine specific DNA recognition, to test these predictions in future experiments, and to find methods to engineer proteins with novel biological functions.
- Fudenberg G, Imakaev M, Lu C, Goloborodko A, Abdennur N, Mirny LA. Formation of Chromosomal Domains by Loop Extrusion.Cell Rep. 15(9):2038-49 (2016)
- Fudenberg G, Abdennur N, Imakaev M, Goloborodko A, Mirny LA Emerging Evidence of Chromosome Folding by Loop Extrusion CSH Symp Quant Biol (2017)
- Gibcus J, Samejima K, Goloborodko A, Samejima I, Naumova N, Nuebler J, Kanemaki MT, Xie L, Paulson JR, Earnshaw WC, Mirny LA, Dekker J A pathway for mitotic chromosome formation.