Silencing Alarms: Discovering How Viruses Evade Our Cellular Immune Systems, Robert LeDesma, G6 (3964620)
The cells in our body inherently possess an alarm system that can detect when an invader, such as a virus, infects the cell. Unfortunately, viruses are constantly evolving ways in which they can silence our cellular alarm systems so that they can wreak havoc undetected. My research focuses on identifying how viruses such as hepatitis E virus (HEV) are able to silence our cellular alarms. One way we can do this is through the biological tenant “form follows function.” If we know how a protein looks, or folds, we can learn a lot about how the protein functions. In the case of silencing a cellular alarm, the virus uses its own set of proteins to accomplish this. I’ve used the new protein folding algorithm AlphaFold to predict how HEV folds its largest protein, and identified regions predicted to use metal ions as scaffolding. This allows the virus to fold in a specific way that allows it to silence the cellular alarms. Using the method inductively-coupled plasma mass spectrometry, I’ve confirmed the presence of the metal ion binding domain. I further identified that mutating some of the amino acids in the metal ion binding domain causes the protein to lose the ability to bind metal ions, causing the protein to fold aberrantly, thus giving us insight into how the protein functions.