Molecular Biologist Sandra Weller Talks about “What’s Possible”

Sandra Weller in her lab at UConn Health where she conducts groundbreaking research on the herpes simplex virus. (Lanny Nagler for UConn Health)

What my research team hopes to make possible is a new therapy to treat a ubiquitous and formidable foe – the herpes simplex virus.

There has been an epic evolutionary battle being waged between viruses and humans for millions of years. Herpes simplex is one of the nastiest and most common viruses that infect humans. It’s found in over two-thirds of the world’s population and is responsible for oral, genital, and sight-threatening eye infections in adults and severe birth defects in infected newborns.

Even though there is a reasonably effective drug, acyclovir, on the market, it was developed 40 years ago and resistance to the drug is fairly common. That’s why my lab is working to gain greater insight into how this virus works so more effective treatments can be developed.

In order to do that, we’ve decided to focus our research on answering two major questions:  How does the herpes simplex virus replicate its genetic material? And how does the virus interact with its human host?

We know that the survival of all organisms depends on their ability to produce an exact copy of their genetic material.  Herpes simplex virus accomplishes this by making eight viral proteins that can assemble into a sophisticated machine capable of performing this complex task. One part of this machine is a helicase that can unwind DNA allowing it to be copied. Another reorganizes the infected cell nucleus and forms a scaffold for the replication machinery.

Herpes simplex virus also makes its own polymerase that copies the DNA. We are very interested in how these proteins interact with one another to assemble the machinery needed for DNA synthesis. Once we understand this machinery, we would like to figure out how to break it.  We want to design chemicals or molecules that can prevent the replication machinery from making new DNA.  These molecules could then be used to treat viral infections.

Our second area of focus is figuring out how the herpes simplex virus interacts with its human host. Viral infections are a threat to host survival and reproduction, and as a result, hosts have evolved a variety of mechanisms to defend themselves. Viruses in turn have adapted to counteract these defensive mechanisms.  Our work has led to the identification of two viral proteins that interact with cellular processes in novel ways to escape antiviral strategies.

By studying this evolutionary arms race, we hope to figure out a way to inactivate the viruses’ counter-defense strategies and in turn – make possible the discovery of better ways to treat viral infections.

Sandra Weller, Ph.D., professor and chair of molecular biology and biophysics at UConn Health, is internationally recognized for ground-breaking discoveries on herpes simplex virus. She is a Board of Trustees Distinguished Professor, the highest faculty honor at the University of Connecticut and was the first female president of the Connecticut Academy of Science and Engineering. As president of the Association of Medical School Microbiology and Immunology Chairs she promotes STEM education, research, and public outreach.