Show simple item record

dc.contributor.advisorLin, Kevin
dc.contributor.authorSchlamowitz, Zachary
dc.creatorSchlamowitz, Zachary
dc.date.accessioned2023-08-17T04:49:49Z
dc.date.available2023-08-17T04:49:49Z
dc.date.issued2023
dc.identifier.citationSchlamowitz, Zachary. (2023). EXAMINING THE LINK BETWEEN PEROXIREDOXIN PROTEINS AND MUTUALLY EXCLUSIVE TRANSCRIPTION FACTOR ACTIVATION WITH A MATHEMATICAL MODEL (Bachelor's thesis, University of Arizona, Tucson, USA).
dc.identifier.urihttp://hdl.handle.net/10150/668720
dc.description.abstractOxidative stress is a fundamental stimulus to which eukaryotic cells respond via many channels. Among these channels are both protein systems that process oxidative stress, such as the 2-Cys peroxiredoxin-thioredoxin system (PTRS), as well as changes in transcriptional activity that target outcomes such as growth, damage control and repair, or cell death. Recent work has revealed connections between the PTRS and temporal phases of transcriptional activity involving famous transcription factors like p53 and FOXO1. To examine potential mechanisms for these connections, we implement an existing dynamical systems mathematical model for the PTRS. We hypothesize that dose-dependent hyperoxidation events enact ultrasensitive switches by which the PTRS can categorize stress severity and activate appropriate transcriptional responses. Using numerical simulations of the PTRS in human cells, we provide a proof of principle for staggered, switchlike hyperoxidation of peroxiredoxins (Prx) as well as an underlying mechanism requiring simultaneous signaling by Prx I and II. Then, we use our model to make testable predictions about individual Prx knockouts as well as the affinity for hydrogen peroxide of Prx across oxidation states. This study provides direction for future experimental work and sheds light into the mechanisms underlying oxidative stress response in human cells.
dc.language.isoen
dc.publisherThe University of Arizona.
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectoxidative stress
dc.subjectperoxiredoxin-thioredoxin system
dc.subjecthyperoxidation
dc.subjectp53
dc.subjectFOXO1
dc.subjectmathematical model
dc.subjectODEs
dc.titleEXAMINING THE LINK BETWEEN PEROXIREDOXIN PROTEINS AND MUTUALLY EXCLUSIVE TRANSCRIPTION FACTOR ACTIVATION WITH A MATHEMATICAL MODEL
dc.typeElectronic thesis
dc.typetext
thesis.degree.grantorUniversity of Arizona
thesis.degree.levelbachelors
thesis.degree.disciplineMathematics
thesis.degree.disciplineHonors College
thesis.degree.nameB.S.
refterms.dateFOA2023-08-17T04:49:49Z


Files in this item

Thumbnail
Name:
azu_etd_hr_2023_0195_sip1_m.pdf
Size:
845.2Kb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record