Determining How S100A9 Activates TLR4 Using Evolutionary and Biochemical Approach

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dc.contributor.advisorHarms, Mike
dc.contributor.authorYin, Jiayi
dc.date.accessioned2021-07-27T16:57:35Z
dc.date.available2021-07-27T16:57:35Z
dc.date.issued2021
dc.description1 page.
dc.description.abstractThe immune system activates inflammation in response to both foreign pathogens and internal damage. Dysregulated inflammation can lead to many chronic diseases such as arthritis, inflammatory bowel disease, and some cancers. S100A9, a protein expressed in immune cells, has been found in high concentration in inflamed tissue of many of these chronic diseases. S100A9 strongly activates TLR4, a proinflammatory receptor, and thus activates pathological inflammation. Understanding how S100A9 interacts with TLR4 would be useful to create therapeutics to treat these diseases. My project is to use evolutionary and biochemical techniques to find out what sequence changes to S100A9 were important in its evolutionary history that led to greater proinflammatory activity. I will characterize modern mammalian S100A9s that diverged more distantly from humans such as koala, platypus, and echidna, using recombinant protein expression and purification of S100A9 proteins from Escherichia coli followed by functional assays in human embryonic kidney cells. I will also characterize mutant ancestral S100A9s to identify important functionally related amino acids of S100A9, using site-directed mutagenesis, and then characterize how these mutations alter activity. I will have identified a few key mutations important for the evolution of S100A9 function, setting up mechanistic studies for how S100A9 activates TLR4 from this research program.en_US
dc.format.mimetypeapplication/pdf
dc.identifier.orcid0000-0002-7233-1568
dc.identifier.urihttps://hdl.handle.net/1794/26489
dc.language.isoen_US
dc.publisherUniversity of Oregon
dc.rightsCC BY-NC-ND 4.0
dc.subjectImmune systemen_US
dc.subjectInflammationen_US
dc.subjectEvolutionen_US
dc.subjectBiochemistryen_US
dc.subjectS100A9, LPS and TLR4en_US
dc.titleDetermining How S100A9 Activates TLR4 Using Evolutionary and Biochemical Approach
dc.typePresentation

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