Presenter: Jiayi Yin – Biochemistry
Faculty Mentor(s): Mike Harms, Sophia Phillips
Session: (In-Person) Poster Presentation
The 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 continue to 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 couple these studies with further characterization of how TLR4 specificity and activity for endotoxin, the pathogenic ligand for which TLR4 evolved to recognize, changed in different species. These data will help us understand how the host protein S100A9 evolved inflammatory activity, and how TLR4 evolved to activate with a variety of ligands.