Viral entry
To enter cells viruses have to fuse their membrane to that of the cells they want to infect. The viruses bind to specific proteins (“receptors”) found on target cells. We use tools in molecular biology (CRISPR-Cas9 genetic screens), protein biochemistry, biophysics, and structural biology (X-ray crystallography and cryo-EM) to identify and then visualize how viruses bind to receptors and infect cells.
Antibody neutralization
Antibodies can prevent viruses from entering cells by (1) blocking attachment to receptors, (2) blocking the conformational changes viral surface proteins undergo to allow for fusion of viral and host cell membranes. Some antibodies act as “decoy receptors” (receptor-mimicking antibodies). The epitopes for antibodies that block conformational changes are usually more conserved but are harder to access because they sit closer to the viral membrane. We isolate from the blood of individuals that have recovered from infections anti-viral monoclonal antibodies. Our goal is to develop cocktails of monoclonal antibodies that can be administered to treat or prevent infection.
Viral Polymerases
Once viruses enter cells, they rely on viral-specific polymerases to transcribe or replicate their genetic material. Viral polymerases are critical drug targets against many RNA and DNA viruses. We use tools in protein biochemistry, biophysics, and structural biology to understand how these polymerases participate in the viral life cycle. By structurally characterizing these viruses, we hope to identify unique and/or conserved features that may serve as suitable drug targets.