Research Projects

Protein transport along DNA is a critical issue in cell biology, with the dominant mechanism being facilitated diffusion. However, recent studies have shown that chromatin is not a simple linear polymer but Topologically Associated Domains (TADs), which are short collapsed regions of the genome with large numbers of spatial contacts between genomically distant segments. Proteins perform a random walk on a connected network topology reflecting the inter-segmental contacts of the chromatin polymer. A less-explored aspect of protein diffusion on DNA is the effect of crowding by other DNA-bound proteins, which may alter search kinetics at physiological densities. This project aims to develop a comprehensive understanding of the role of chromatin structure, topology, and crowding on protein transport times and search strategies on real biological chromatin using stochastic processes, random walks, and first passage times distributions. The scientific objectives include understanding the role of network connectivity on search times and exit time distributions, the role of crowding by DNA-bound proteins on protein first passage times, and the role of protein kinetics in generating and maintaining the network topology of chromatin through simulations of loop extrusion factor protein motion on chromatin. Successful completion of these objectives will transform our understanding of protein transport of biological chromatin. The predictions made from theoretical and simulation studies can be tested experimentally in labs to ascertain the importance of the structure and topology of chromatin on protein transport.