Term | Value | Language |
---|---|---|
dc.contributor.advisor | Harms, Mike | |
dc.contributor.author | Brown, Corinthia | |
dc.date.accessioned | 2024-08-30T19:10:12Z | |
dc.date.available | 2024-08-30T19:10:12Z | |
dc.date.issued | 2024 | |
dc.identifier.uri | https://scholarsbank.uoregon.edu/xmlui/handle/1794/29890 | |
dc.description | 61 pages | |
dc.description.abstract | Inflammation is a vital process our bodies use to remove foreign entities and help restore function to damaged tissue. However, when inflammation excessively activates it can lead to arthritis, neurodegeneration, and sepsis, which contributes to 11 million deaths a year. Inflammation results from inflammatory cytokines produced by the NF-kB pathway, activated by Toll-Like Receptor 4 (TLR4). We know that certain lipopolysaccharides (LPS) present on gram-negative bacteria drive the dimerization of TLR4 and activate inflammatory cytokine production. However, we do not completely understand the rules which govern TLR4 activation, making it difficult to control this regulator of inflammation, particularly in clinical applications. To understand how TLR4 activates, the Harms lab studies the alterations in function throughout this protein’s evolutionary history. However, when the TLR4 in question is far from humans on the phylogenetic tree we experience difficulties observing the protein’s activation. To observe distant species’ TLR4 activities we developed a method which allows the outer portion (ectodomain) of the protein to bind to its specific ligand yet have an inner portion (transmembrane and TIR domain) which allows for interactions with the human proteins which bridge the connection between TLR4 and the inflammatory pathway. | en_US |
dc.language.iso | en_US | |
dc.publisher | University of Oregon | |
dc.rights | CC BY 4.0 | |
dc.subject | TLR4 | en_US |
dc.subject | Helix Shifting | en_US |
dc.subject | Protein Evolution | en_US |
dc.subject | Internal Signaling Mismatch | en_US |
dc.subject | Protein Cassette | en_US |
dc.title | ANALYZING LIGAND SPECIFICITY TO ASSESS THE EVOLUTION OF TLR4 | |
dc.type | Thesis/Dissertation | |
dc.identifier.orcid | 0009-0002-0920-6884 |