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dc.contributor.advisorRon Weiss.en_US
dc.contributor.authorTordoff, Jesse(Jessica Jane)en_US
dc.contributor.otherMassachusetts Institute of Technology. Computational and Systems Biology Program.en_US
dc.date.accessioned2020-09-15T21:54:43Z
dc.date.available2020-09-15T21:54:43Z
dc.date.copyright2020en_US
dc.date.issued2020en_US
dc.identifier.urihttps://hdl.handle.net/1721.1/127373
dc.descriptionThesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, May, 2020en_US
dc.descriptionCataloged from the official PDF of thesis.en_US
dc.descriptionIncludes bibliographical references (pages 114-124).en_US
dc.description.abstractThe shapes and structures created by living organisms have properties that any engineer would desire: they are self-healing, growing, adaptive, and range in complexity and material property from the strength of bone to the lightweight flexibility of an insect wing. The goal of this thesis is to use synthetic biology to design, control, and understand the range of structures that can be constructed using a ubiquitous tool for self-organization in animal development: cell sorting. We first use experiments and computational modeling to demonstrate how incompletely sorted structures can be systematically designed by quantitative control of cell composition. By varying the number of highly adhesive and less adhesive cells in multicellular aggregates, we find that cell type ratio and total number of cells are controllers of pattern formation, and the resulting structures are maintained over the course of days.en_US
dc.description.abstractNext, we establish a set of design rules for cell sorting-driven shape assembly using cell lines with engineered genetic circuits that can induce expression of different cadherins. We show that, even when well mixed, populations of cells with different cadherin expression profiles sort themselves in predictable ways. The resulting shapes vary significantly, including planes of semi-regular polka dots, a sphere engulfed by an outer shell, maze-like intertwined populations, and radial protrusions from a core. We can reliably select between these shapes and control their properties by changing induction of cadherin expression, population ratio, cadherin identity, and total aggregate size. Finally, we have designed and constructed a recombinase-based tool to break symmetry in a population of cells, with the ultimate goal of controlling the autonomous creation of different subpopulations from a single cell.en_US
dc.description.abstractBy creating a platform to programmably generate multicellular forms, this thesis aims to establish design principles for synthetic morphogenesis and provide a framework to control living shapes.en_US
dc.description.statementofresponsibilityby Jesse Tordoff.en_US
dc.format.extent124 pagesen_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsMIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582en_US
dc.subjectComputational and Systems Biology Program.en_US
dc.titleEngineering self-assembling living structures with mammalian synthetic biologyen_US
dc.typeThesisen_US
dc.description.degreePh. D.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Computational and Systems Biology Programen_US
dc.identifier.oclc1192538645en_US
dc.description.collectionPh.D. Massachusetts Institute of Technology, Computational and Systems Biology Programen_US
dspace.imported2020-09-15T21:54:43Zen_US
mit.thesis.degreeDoctoralen_US
mit.thesis.departmentCSBen_US


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