New Frontiers: Christopher Barnes

When Christopher Barnes began his postdoctoral studies with Pamela Bjorkman at the California Institute of Technology in 2017, the HIV field was decades old and crowded with eminent researchers like his then-new mentor. But Barnes was struck by how much remained to be learned about the virus, and by the innovative research being done by Bjorkman and her collaborator, Michel Nussenzweig at The Rockefeller Institute, both of whom were HHMI Investigators. (Bjorkman is now an Investigator Emeriti). “Michel had recently discovered a new class of antibody,” Barnes explains. Antibodies are proteins that circulate in our blood, targeting foreign pathogens. In the case of HIV, there are some that stop the virus from entering or attaching to the host cell. When he saw how the antibody interacted with HIV, Barnes “realized that there’s still so much we don’t know about this virus." He explains, "This work from a few years ago shows that we are still identifying new classes of antibodies that may be useful in vaccine development.” Applying Advanced Structural Biological Techniques to the Study of HIV Barnes was awarded a Hanna Gray Fellowship in 2017, while still in Bjorkman’s lab. He is now an assistant professor of biology and Sarafan ChEM-H Institute Scholar at Stanford University. His lab uses advanced structural biological techniques, including crystallography and electron microscopy, to study how HIV makes first contact with host cells – and how the immune system responds. “There’s a protein that sits on the surface of the virus that looks for the proteins or receptors on our host cells, which it can bind to,” Barnes says. “And just like in COVID, when it binds to that receptor, it initiates a process that allows the viral membrane to fuse with the host membrane, delivering genomic information into our cells that lead to infection.” Stopping that process – and thus, preventing infection – is Barnes’s main work, and the Hanna Gray Fellowship has helped him think more ambitiously. “The Hanna Gray Fellowship allows me to explore these technologies and techniques, even ones that I’m not formally trained in,” Barnes says. “I learn new skills and immediately see how they could be applied to work in my lab, not only in the study of HIV but across different viral families that we’re researching. These new approaches can lead to vaccines, of course, but they also expand our knowledge of the basic science of these viruses.” “This field requires a lot of creativity,” he says. “There are new ways to think about HIV and vaccine development, leveraging technologies that did not exist even three years ago when I started my lab at Stanford. Now, we can design proteins that behave how we want, utilize new computational tools that can help us understand how antibodies evolve, and use this information to develop vaccines that drive the desired immune system response. As a protein engineer, it’s a remarkable space to be in. How can we design proteins or vaccines that manipulate the immune system to produce the exact antibody sequence we want? We can’t be afraid to take the risk and try something that’s really off the wall to tackle this problem.” Barnes’s research could identify how to promote antibody evolution in the immune system that potentially prevents HIV infection. But the new perspectives on immunity will be beneficial whether a cure arrives or not.