Research Projects

The hierarchical assembly of chromatin results in interesting polymer organization and polymer properties. While recent experiments have uncovered a lot about the static 3D organization of the chromatin polymer, very little is known about the dynamics of chromatin. How this hierarchical assembly emerges and how it is maintained are questions of great current interest. Within the nucleus, the extent of chromatin condensation is closely linked to transcriptional activity: heterochromatin is more condensed and transcriptionally repressed, whereas euchromatin is less condensed and transcriptionally active. These domains are established and maintained with the assistance of ATP-dependent chromatin remodelers, which facilitate nucleosome sliding, dissociation, and rebinding—processes critical for the formation and maintenance of euchromatin and heterochromatin regions. In an attempt to understand the organisational changes induced by these remodelers, extensive in vitro studies have been conducted using short chromatin filaments. These experiments provide an ideal platform for modelling studies. 1: In this study, building on our earlier studies on chromatin dynamics, we propose to employ hybrid Molecular Dynamics-Monte Carlo simulations to investigate an active multipolymer system that incorporates nucleosome sliding, dissociation, and rebinding. Some specific questions we will be asking are 1) How does the placing of nucleosomes along the DNA affect the properties of the condensate they form? and 2) How do these properties change when ATP is added to the buffer to facilitate nucleosome sliding and disassembly-assembly processes? 2: In successive cycles the cell progresses from mitosis to interphase and to the subsequent mitosis. During this cycle, the genome in the cell nucleus replicates, condense, and get separated. However, the memory of the structural organisation of the genome in the parent cell is retained by the daughter cells. Since during interface the chromosomes do not move much, the large scale ( chromosome territories) memory should be mostly retained during the mitosis, while smaller scale domain structures ( Topological associated domains) are lost during duplication. In a recent work Fujishiro and Sasai have developed a basic model to study this problem of memory. We plan to develop this further by incorporating the known information on histone markers and other parameters consistent with the observed contact probabilities, in a multi-scale model.