High-Throughput Discovery of Input Stimuli of Bacterial Two-Component Systems

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dc.contributor.advisorTabor, Jeffrey J.en_US
dc.contributor.committeeMemberMartí, Angel A.en_US
dc.creatorBrink, Kathryn Reneeen_US
dc.date.accessioned2021-08-16T19:17:24Zen_US
dc.date.available2022-08-01T05:01:12Zen_US
dc.date.created2021-08en_US
dc.date.issued2021-07-22en_US
dc.date.submittedAugust 2021en_US
dc.date.updated2021-08-16T19:17:24Zen_US
dc.description.abstractTwo-component systems (TCSs) are the largest class of biological signal transduction pathways and an important class of bacterial sensors. In their native contexts, TCSs enable bacteria to sense and respond to changes in their environment. TCSs are also a major source of novel biosensors for medical, environmental, and industrial applications. In the first portion of this work, we use TCS engineering and chemical input screens to characterize TCSs of unknown function from Shewanella oneidensis. Through these screens, we discover a pH-responsive TCS, which we apply to detect acidification of intestinal tissues in a mouse model of inflammatory bowel disease. In the second portion of this work, we develop a high-throughput screening approach for characterizing peptide-TCS interactions. We screen PhoPQ, a virulence-regulating TCS from Salmonella Typhimurium, against 117 human antimicrobial peptides (AMPs). We discover 13 novel activators of PhoPQ comprising diverse sequences, structures, and biological functions and identify subdomains and peptide biophysical features responsible for PhoPQ activation. Finally, we find that PhoPQ homologs exhibit distinct AMP response profiles, suggesting a role for evolutionary adaptation in AMP sensing. The engineering approaches developed here enable high-throughput discovery and characterization of TCS inputs, which could provide important insights into bacterial stimulus response and reveal novel biosensors with applications across a wide range of sectors.en_US
dc.embargo.terms2022-08-01en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationBrink, Kathryn Renee. "High-Throughput Discovery of Input Stimuli of Bacterial Two-Component Systems." (2021) Diss., Rice University. <a href="https://hdl.handle.net/1911/111191">https://hdl.handle.net/1911/111191</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/111191en_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.subjecttwo-component systemen_US
dc.subjectsynthetic biologyen_US
dc.subjectbiosensoren_US
dc.titleHigh-Throughput Discovery of Input Stimuli of Bacterial Two-Component Systemsen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentSystems, Synthetic and Physical Biologyen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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