Research
Applying an integrative structural virology approach to understand how viruses alter mitochondrial function.
In the Rafie lab, we aim to elucidate the mechanisms through which viruses modify mitochondria to facilitate viral replication and leverage this knowledge to identify novel targets for antiviral therapeutics. Our primary focus is on DNA viruses, such as human adenoviruses and human herpes viruses, which alter mitochondrial functions including innate immunity and metabolism, as well as organelle structure. To achieve our goals, we employ a comprehensive integrated structural biology approach. This includes macromolecular x-ray crystallography, single-particle cryogenic electron microscopy, and in situ cryogenic electron tomography, complemented by techniques from biochemistry, biophysics, cell biology, and virology. Key projects in our lab in volve the recombinant expression and purification of viral and host proteins from bacterial or eukaryotic expression systems. These purified proteins are then biochemically and structurally characterized to facilitate high-throughput compound screening, aimed at identifying molecules that can be developed into highly selective and potent antiviral compounds through structure-guided drug development. Additionally, we investigate viral agents that hijack and alter host cell processes. This is done by expressing these agents in adherent cell lines and using fluorescence microscopy to observe cellular changes. Significant events are then examined in greater detail using in situ cryogenic electron tomography. This integrative approach positions us to develop novel, next-generation antiviral therapeutics.