The physics of cell-fate choice

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dc.contributor.advisorLevine, Herberten_US
dc.contributor.advisorIgoshin, Oleg Aen_US
dc.creatorTripathi, Shubhamen_US
dc.date.accessioned2022-09-23T16:27:00Zen_US
dc.date.available2022-09-23T16:27:00Zen_US
dc.date.created2022-08en_US
dc.date.issued2022-07-26en_US
dc.date.submittedAugust 2022en_US
dc.date.updated2022-09-23T16:27:00Zen_US
dc.description.abstractMulticellular organisms are composed of many different cell types. All such cells arise from a single cell--- the zygote--- and acquire the various cell fates seen in adult organisms. The different cell types are characterized by distinct, cell-fate-specific gene expression patterns. Cells of different types can also exhibit varying metabolic states depending on their intrinsic needs and the nutrient microenvironment. Both during development and in adult organisms, cell-fate choice is tightly controlled, and its dysregulation is known to contribute to many pathologies, including cancer. In this thesis, I describe our simulations-based efforts to identify certain general principles underlying cell-fate choice. Throughout, I discuss how such regulation can go awry in a disease like cancer, leading to the emergence of aberrant cell fates. First, I describe a spin glass-based theory of minimal frustration in regulatory networks implicated in cell-fate choice, and show that the minimal frustration property is key to the robust establishment and maintenance of biological cell-fates. The minimal frustration property is also crucial to the success of various systems biology models of cell-fate choice. Next, I present two models concerning noise in cell-fate choice--- a mechanical model of DNA supercoiling-mediated transcriptional noise and a coarse-grained model of noise in partitioning during cell division that can create and maintain a phenotypically heterogeneous population. Finally, I describe a mechanistic model of the key metabolic pathways active in tumors and other fast-proliferating cells. Our model recapitulates tumor cell behavior across contexts and makes useful predictions concerning the ways tumor cells can evade metabolic therapies. Overall, this thesis describes multiple examples of how physical and systems biology-based approaches can be leveraged to understand the key principles underlying cell-fate choice across biological contexts.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationTripathi, Shubham. "The physics of cell-fate choice." (2022) Diss., Rice University. <a href="https://hdl.handle.net/1911/113250">https://hdl.handle.net/1911/113250</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/113250en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectcell-fate choiceen_US
dc.subjectgene networksen_US
dc.subjectfrustrationen_US
dc.subjectcoarse grainingen_US
dc.subjectDNA supercoilingen_US
dc.subjectpartitioning noiseen_US
dc.subjectWarburg effecten_US
dc.subjecttumor metabolismen_US
dc.titleThe physics of cell-fate choiceen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentSystems, Synthetic and Physical Biologyen_US
thesis.degree.disciplineEngineeringen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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