A study of bacterial chromosome organization using bead spring polymer models

Abstract

The chromosome a long polymer sim 2 m in the human cell and sim 1 mm in a bacterial cell consists of all the genetic information and is packed sim 1000 fold inside the nucleus in a human cell or in the bacterial cell The chromosome is involved in various cellular processes e g DNA replication transcription and is not like a random walk polymer but shows a unique spatial organization at mu length scales as is evident from the recent experimental studies The contact map generated from the experimental technique Hi C gives the frequency of two chromosome segments of 1 kilo base pair 1 mega base pair each to be in proximity to each other The Hi C contact maps which give essential insights about the chromosome organization but do not provide the overall 3D structure of the chromosome Also despite several theoretical and experimental efforts the mechanism leading to the mu length scale organization of the chromosome remains elusive Currently the primary challenge in the field is to build a physical model of the chromosome that can predict the 3D organization and shed light on the mechanism in the chromosome organization obtained in the Hi C contact map Developing such a model requires statistically significant high throughput data from individual cells with close dialogue between modeling and experiment Here in this thesis we use bead spring model of the ring polymer to understand the role of different physical mechanisms e g DNA binding proteins the crowding environment due to various proteins enzymes inside the cell release of topological constraints and the confinement of the cell wall in the chromosome organization of bacteria E coli and C crescentus We also predict the overall 3D organization of the chromosome and validate our prediction with the available experimental data In particular we use the data from the Hi C contact map of E coli and C crescentus to introduce the cross links at particular positions in the bead spring polymer whereone coarse grained bead represents 1000 base pairs BP newline newline