THEORETICAL AND COMPUTATIONAL STUDIES OF HUMAN INTERPHASE CHROMOSOMES

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dc.contributor.advisorThirumalai, Devarajanen_US
dc.contributor.authorShi, Guangen_US
dc.contributor.departmentBiophysics (BIPH)en_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2019-09-27T05:35:09Z
dc.date.available2019-09-27T05:35:09Z
dc.date.issued2019en_US
dc.description.abstractIn this thesis, various aspects of dynamical and structural properties of human interphase chromosomes are studied using both theoretical and computational tools. In addition, the cooperative transport by the multi-motor system was investigated using a stochastic kinetic model. First, I create the Chromosome Copolymer Model (CCM) by representing chromosomes as a copolymer. I first showed that the model is consistent with current experimental data. Using the CCM, I further investigated the dynamics of human interphase chromosomes. The model suggested that human interphase chromosome exhibit glassy-like dynamics characterized by sluggish movement, large loci-to-loci variations, and dynamical heterogeneity. Furthermore, I predicted that human interphase chromosomes also display extensive structural heterogeneity. Using a theoretical framework I developed based on polymer physics, I am able to identify that the existence of subpopulations is the reason for the Hi-C-FISH paradox. As an application of the theory, the information of subpopulations of cells can be readily extracted from experimental FISH data. The results suggest that heterogeneity is pervasive in genome organization at all length scales, reflecting large cell-to-cell variations. Then I proceed to develop a method to reconstruct the three-dimensional genome structure directly from Hi-C data. By applying the theory combined with various manifold embedding methods to experimental Hi-C data, I am able to visualize the averaged global 3D organization of a single chromosome and also local structures such as Topological Associated Domains. The method provides a fast and simple way to help experimentalist visualize the genome organization from the measured Hi-C data. Finally, I propose a kinetic model for the multi-motor system. I investigate the effect of mechanical coupling between multiple motors on their velocity and force-velocity behavior. Reduction of velocity is observed for coupled motor system especially when the coupling strength is strong. The model also shows that the multi-motors system is more efficient for transporting large cargo but is less efficient for transporting small cargo compared to a single motor.en_US
dc.identifierhttps://doi.org/10.13016/wpa3-g4fr
dc.identifier.urihttp://hdl.handle.net/1903/24999
dc.language.isoenen_US
dc.subject.pqcontrolledBiophysicsen_US
dc.subject.pquncontrolledchromatin dynamicsen_US
dc.subject.pquncontrolledchromosome organizationen_US
dc.subject.pquncontrolledglassy dynamicsen_US
dc.subject.pquncontrolledmolecular dynamicsen_US
dc.subject.pquncontrolledmolecular motoren_US
dc.subject.pquncontrolledpolymer modelen_US
dc.titleTHEORETICAL AND COMPUTATIONAL STUDIES OF HUMAN INTERPHASE CHROMOSOMESen_US
dc.typeDissertationen_US

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