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dc.contributor.authorGencer, Gozde
dc.date.accessioned2019-10-15T16:51:18Z
dc.date.available2021-08-29T06:00:17Z
dc.date.issued2019-08-30
dc.identifier.otherGencer_cornellgrad_0058F_11614
dc.identifier.otherhttp://dissertations.umi.com/cornellgrad:11614
dc.identifier.otherbibid: 11050740
dc.identifier.urihttps://hdl.handle.net/1813/67754
dc.description.abstractHuman gastrointestinal (GI) tract is a long hollow tube, connecting mouth, esophagus, stomach, small intestine, large intestine, and anus. Two main functions of GI tract are food digestion and nutrient absorption. Moreover, it is the largest immune organ because the lumen of this hollow tube has the largest surface area for the contact between the outside world and internal body environment. This provides an extensive interface for colonization of microorganisms, referred as gut microbiota. Probiotic and commensal bacteria, which are important components of this microbial community, have profound effects on human health, including immunity, metabolism, and gut-brain axis. Thus, these organisms can be utilized to develop next-generation microbiota-based therapeutics. In this dissertation, we focused on harnessing probiotic and commensal Escherichia coli strains as novel therapeutics for hyperuricemia and Crohn’s disease. Particularly, we reprogrammed these bacteria via genetic engineering for detection and elimination of disease biomarkers through human GI tract. In the first project, our goal was to reprogram probiotic and commensal E. coli strains to develop a novel system for accurate diagnosis and effective long-term management of hyperuricemia. To achieve this goal, we constructed (i) a synthetic promoter sequence that can detect the changes in uric acid in a dose-dependent manner, (ii) a uric acid degradation module that can eliminate the excess uric acid in the intestine, and (iii) an in vitro model with human intestinal cell line, Caco-2, that provided a versatile tool to study uric acid transport and degradation. In the second project, our goal was to build a bioreporter monitoring early stages of Crohn’s disease, which is characterized by elevated IFN-γ levels in the intestine. To achieve this goal, we investigated the potential of two signal transduction systems in commensal E. coli for IFN-γ detection: (i) optimization of a previously developed OmpA-OprF chimeric protein- and pspA-dependent biosensor, and (ii) development of a GacS/GacA- and rsmZ-dependent biosensor, which is adapted from Pseudomonas aeruginosa PAO1. These synthetic gene circuits and signaling systems provided an essential contribution for in situ detection and elimination of human disease biomarkers through GI tract.
dc.language.isoen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectE. coli
dc.subjectCrohn's Disease
dc.subjectHyperuricemia
dc.subjectIFN-γ
dc.subjectUric Acid
dc.subjectMicrobiology
dc.subjectBioengineering
dc.subjectsynthetic biology
dc.titleEngineering Probiotic and Commensal Bacteria for Detection and Elimination of Disease Biomarkers Through Human Gastrointestinal Tract
dc.typedissertation or thesis
thesis.degree.disciplineBiological and Environmental Engineering
thesis.degree.grantorCornell University
thesis.degree.levelDoctor of Philosophy
thesis.degree.namePh.D., Biological and Environmental Engineering
dc.contributor.chairMarch, John C.
dc.contributor.committeeMemberPeters, Joseph E.
dc.contributor.committeeMemberWinans, Stephen C.
dcterms.licensehttps://hdl.handle.net/1813/59810
dc.identifier.doihttps://doi.org/10.7298/jzgb-k107


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