A theranostic bio-device for biomedical applications

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buir.advisorŞeker, Urartu Özgür Şafak
dc.contributor.authorHacıosmanoğlu, Nedim
dc.date.accessioned2019-08-26T08:09:34Z
dc.date.available2019-08-26T08:09:34Z
dc.date.copyright2019-08
dc.date.issued2019-08
dc.date.submitted2019-08-23
dc.descriptionCataloged from PDF version of article.en_US
dc.descriptionThesis (M.S.): Bilkent University, Department of Materials Science and Nanotechnology, İhsan Doğramacı Bilkent University, 2019.en_US
dc.descriptionIncludes bibliographical references (leaves 95-104).en_US
dc.description.abstractBiological systems are programmable by their nature. With using the abilities of these systems, scientists have designed, engineered and repurposed living machines for various tasks including biological sensing, recording of cellular events, drug production and disease treatment. Compared to the current methodology for these tasks, engineering biological systems provide a promising tool for the future of medicine, especially in the case of disease treatment. Type II Diabetes Mellitus (T2DM) is a medical condition which occurs by the deficiency of insulinotropic hormones inside the body, and affects nearly half billion people worldwide. Treatment strategies for this disease includes monitoring patient for blood glucose levels, fine production of insulinotropic hormones and providing dose-controlled treatment for the patients. All these operations increase the cost of the treatment and cause a global problem for both medical professionals and the patients. In this thesis, we propose novel systems for developing theranostic strategies for T2DM by using synthetic biology principles and genetically controlled sense-and-response cascades inside living cells. Proposed systems include a whole-cell glucose biosensor module, which can detect glucose concentrations by using internal glycolysis machinery of a probiotic Escherichia coli (E. coli) bacteria, and a release module, which can controllably secrete therapeutic molecules from the E. coli cell surface. To do that, we engineered an enzyme based biosensor module which takes the pyruvate synthesized as a result of glycolysis and turns that molecule into hydrogen peroxide via SpxB pyruvate oxidase enzyme to later detect that signal with an optimized hydrogen peroxide biosensor. In order to later incorporate this biosensor with a release mechanism, we designed and engineered an Antigen-43 (Ag43) autotransporter based peptide release system. In that system, we used Ag43 autotransporter fused GLP-1 peptide, an insulinotropic hormone for the type II diabetes treatment that is controllably displayed on the cell surface. Another Ag43 fused protein, TEV protease, with a different control mechanism is also cooperated in the system to release GLP-1 from the surface by cutting the peptide from its recognition site. Taking the ability of glucose sensing and the successfully engineered release mechanisms, our proposed system has a huge potential to be used as an alternative system for treatment of the T2DM.en_US
dc.description.provenanceSubmitted by Betül Özen (ozen@bilkent.edu.tr) on 2019-08-26T08:09:33Z No. of bitstreams: 1 Nedim_Haciosmanoglu_MSc_Thesis_Signed.pdf: 9713933 bytes, checksum: 80732ab0be06f712bdc3c4fc5208c590 (MD5)en
dc.description.provenanceMade available in DSpace on 2019-08-26T08:09:34Z (GMT). No. of bitstreams: 1 Nedim_Haciosmanoglu_MSc_Thesis_Signed.pdf: 9713933 bytes, checksum: 80732ab0be06f712bdc3c4fc5208c590 (MD5) Previous issue date: 2019-08en
dc.description.statementofresponsibilityby Nedim Hacıosmanoğluen_US
dc.embargo.release2020-02-23
dc.format.extentxxi, 155 leaves : illustrations, charts (some color) ; 30 cm.en_US
dc.identifier.itemidB108219
dc.identifier.urihttp://hdl.handle.net/11693/52370
dc.language.isoEnglishen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectSynthetic biologyen_US
dc.subjectWhole cell biosensoren_US
dc.subjectProtein releaseen_US
dc.subjectLiving therapeuticsen_US
dc.titleA theranostic bio-device for biomedical applicationsen_US
dc.title.alternativeBiyomedikal uygulamalar için teşhis ve tedavi biyo-aracıen_US
dc.typeThesisen_US
thesis.degree.disciplineMaterials Science and Nanotechnology
thesis.degree.grantorBilkent University
thesis.degree.levelMaster's
thesis.degree.nameMS (Master of Science)

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