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Biophysicist in Profile

Christopher Barnes

Christopher Barnes

June 2020 // 8295

When Christopher Barnes was a child, he wanted to be a chef — but not just any chef — a great one. “My mom likes to tell everyone the story of how I used to watch The Great Chefs of the World and make shopping lists for her so I could recreate the dishes I saw,” he shares. “Obviously I didn’t know how much some of the things on my list cost, as I was asking for truffles, wines, and other ingredients to recreate Michelin star dishes.” He has similarly striven for greatness to his career in science, now serving as a HHMI Hanna Gray Postdoctoral Fellow at Caltech.  

Christopher Barnes, HHMI Hanna Gray Postdoctoral Fellow at the California Institute of Technology, always enjoyed science. As a teenager, he was a member of STEM clubs and competed in Science Olympiad. He planned to become a medical doc­tor, so upon entering college at University of North Carolina, Chapel Hill (UNC), he studied chemistry and biology to start building toward his goal. At the end of his sophomore year, he inquired about undergraduate research opportunities. “It was at this point that my life changed forever, as I joined the lab of my first mentor, Gary Pielak,” he says. “Gary instilled in me a desire to pursue scientific research and introduced me to the challenges of biophysical research by developing methods for in-cell nuclear magnetic resonance (NMR) spectroscopy. His lab single-handedly put me on the path towards a scientific career in biochemistry and biophysics.”

Pielak remembers his then-graduate student Lisa Charlton rav­ing about Barnes, who was a student of hers in a teaching lab. “Lisa would not stop going on about Christopher Barnes, and that I must recruit him as an undergraduate research assis­tant. I did. He soon earned co-authorship on a key paper about crowding and protein stability in his senior year,” he shares. The projects they worked on involved protein NMR of macromolec­ular crowding in vitro and in living cells. “One of the coolest ef­forts involved bolting a globular protein to a disordered protein. We could observe the disordered part in cells, but the globular part remained invisible,” Pielak explains.

“Christopher’s goal was to attend grad school, but playing Division 1 football and being a BS chemistry major is hard on the GPA, even for a star. I suggested he stay on and earn a master’s degree, which forgives a lot of sins. After three more papers (in about a year), two of them as first author, Christo­pher left triumphant for Pitt,” he says. “Christopher has many admirable qualities as a biophysicist: high intellectual horse­power combined with a normal-sized ego, unafraid of hard work, a reluctance to give up, the ability to listen, and ‘cheerful in all weathers.’ I wish I was still working with Christopher. Hope springs eternal.”

Following his master’s degree in chemistry at UNC, Barnes be­gan a PhD program in molecular pharmacology at the Univer­sity of Pittsburgh. His work there set him on the path into his current field of study. “As a structural biologist and biochemist, I use electron microscopy and X-ray crystallographic tech­niques to investigate interactions between proteins involved in signaling and disease pathogenesis. I got interested in this type of research during my PhD in molecular pharmacology, when I worked under the tutelage of Guillermo Calero in the molecular biophysics and structural biology program,” Barnes shares. “My work focused on resolving fundamental questions about the mechanism by which the general transcription factors regulate RNA Polymerase II (Pol II) activity. Due to the size and complexity of such systems, I had to utilize unique techniques to reconstitute and achieve high-resolution structural infor­mation. I purified, assembled, and crystallized Pol II complexes for data collection at synchrotron and X-ray free electron laser sources, while also developing transmission electron microsco­py methods.”

During graduate school, Barnes and his wife, who is also a biophysicist, became parents to two sons. Balancing new par­enthood and a PhD program was a very difficult undertaking. “Learning how to balance work and life was a challenge, but I faced it by learning how to ask for help. I think most of life’s challenges are not meant to be faced alone and it’s okay to reach out to those around you, as well as family, to help when things seem overwhelming,” he says.

The experience of parenting, especially as his children get older, has deepened his admiration for his parents. “They provided my siblings and me with a great childhood and the tools we needed to succeed in life, while working and being present for all of our activities. I didn’t appreciate how much running around they had to do with us and our activities until my kids started playing soccer,” he says. “When we started having to shuttle kids between parks for games, multiple practices a week, on top of working, I developed a better appreciation for my parents and definitely admire what they did for us.”

Currently, Barnes is a HHMI Hanna Gray Postdoctoral Fellow in the lab of Pamela Bjorkman at Caltech, investigating the structural correlates of antibody-mediated neutralization of HIV-1, and more recently, SARS-CoV-2, the coronavirus that causes COVID-19. “Using crystallographic and single-particle cryo-EM techniques I hope to gain a better understanding of how antigens interact with host receptors, and how antibodies latch onto viral proteins to prevent infection. By understand­ing these interactions with structural biology, I hope to design antibody-therapies, as well as HIV-1 immunogens capable of eliciting a protective response in vaccination.”

Bjorkman shares, “Christopher had been working on deter­mining the structural correlates of virus neutralization by antibodies directed against the envelope protein (Env) of HIV-1 using a variety of techniques including X-ray crystallography (both using conventional synchrotron radiation and X-ray free electron lasers) and single-particle cryo-EM. He is now leading an analogous effort in my lab to use structural biology to exam­ine antibody recognition of the coronavirus spike protein — the analog of HIV-1 Env.”

“I think biophysics is very intriguing and provides explanations for the world around us, at the molecular level. Very few disci­plines have that ability and I think it’s fantastic that when we solve structures we can see why protein X is interacting with protein Y and why compound Z disrupts this interaction,” he shares. “Solving novel structures is one of the best things ever, especially from macromolecular crystals. There is this buildup of anticipation where you don’t know what will happen when these crystals you’ve worked so hard to optimize are exposed to X-rays. Then you see it, this beautiful diffraction pattern to high resolution. I don’t think many things can beat that feeling of not only joy, but relief that all that work wasn’t in vain. As I do more cryo-EM, I’m beginning to have those same moments, when you finally see your particle distribution in the vitrified ice and know that it’s going to be a good data collection day.”

He is now on the academic job market, looking forward to starting his own lab at a leading research institution. “I hope to establish a research program focused on the structure-based design of therapeutics targeting protein complexes involved in infectious disease,” he says. “I hope that my future work and lab will inspire the next-generation of scientists, especially indi­viduals of color who may not feel like they belong in our field.”

Barnes is a new member of the Biophysical Society, and has enjoyed committee and local events. “The fact that the Bio­physical Society provides resources and helps promote local organizations and events is great,” he says. “Being a member has provided me an opportunity to present my research in a forum with experts in my field, while allowing me to expand my network. At the 2020 BPS Annual Meeting I got to meet face-to-face individuals who I’ve only communicated with online, which was a fantastic experience.”

His favorite thing to do outside of work is spend time with his sons, “who I love more than anything in this world.” He and his wife spend a lot of time supporting their interests in sports, robotics, chess, math, and art, and they also enjoy cooking and playing video games together. He jokes, “I find it hilarious when they think they can beat me in Madden or NBA 2K, but I know one day they will, so I’ll just enjoy it for now.”

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