Design of artificial genetic networks to regulate the biosynthesis of polyhydroxyalkanoate copolymers with desirable structures

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dc.contributor.advisorZygourakis, Kyriacosen_US
dc.creatorIadevaia, Sergioen_US
dc.date.accessioned2009-06-03T19:51:58Zen_US
dc.date.available2009-06-03T19:51:58Zen_US
dc.date.issued2008en_US
dc.description.abstractThe design of artificial genetic networks constitutes a powerful tool to regulate cellular physiology. Simple regulatory structures comprised of a few interacting genes can be assembled to engineer desirable phenotypes and control the biosynthesis of end products of biomedical and/or biotechnological interest. This doctoral thesis has focused on the in silico design of artificial genetic networks to drive the biosynthesis of a specific product of biotechnological interest, namely, PHA copolymer chains with desirable structures. In order to understand this complex process, a mathematical model was developed to describe the coupling between the dynamics of polymer and monomer formation and those of the genetic networks. The modeling studies have focused on the utilization of two synthetic networks, known as the genetic toggle and repressilator. The results indicate that the bistable toggle allows regulating the monomer composition of PHA copolymers. The use of the repressilator offers a higher level of control, as it enables the synthesis of PHA block copolymers with different length and composition of each of the blocks that comprise the chains. Additional computational studies have revealed the possibility to achieve superior performance than that of the repressilator, through the design of a novel genetic network that exhibits oscillatory dynamics with minimal overlap amongst gene expression levels. The oscillations were also found to be robust to stochastic fluctuations. Finally, an existing mathematical model was modified to explain the discrepancy of the original repressilator model with experimental data. The modeling studies support the hypothesis that non-specific interactions may also be present in addition to the original three promoter-repressor interactions, which the repressilator was designed to include.en_US
dc.format.extent206 p.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.callnoTHESIS CH.E. 2008 IADEVAIAen_US
dc.identifier.citationIadevaia, Sergio. "Design of artificial genetic networks to regulate the biosynthesis of polyhydroxyalkanoate copolymers with desirable structures." (2008) Diss., Rice University. <a href="https://hdl.handle.net/1911/22254">https://hdl.handle.net/1911/22254</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/22254en_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.subjectChemical engineeringen_US
dc.titleDesign of artificial genetic networks to regulate the biosynthesis of polyhydroxyalkanoate copolymers with desirable structuresen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentChemical Engineeringen_US
thesis.degree.disciplineEngineeringen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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