Biophysical Society Bulletin | October 2020

Biophysicist in Profile

BradleyWebb Areas of Research Cell biology and biochemistry of metabolic enzymes

Institution West Virginia University

At-a-Glance

Bradley Webb , assistant professor in the Department of Biochemistry at West Virginia University, says he “kind of fell into science as a career.” Growing up in Alberta, Canada, he gained a love of science and nature from his mom, and inherited analytical and mechanical skills from his dad. “My mom got me my first microscope when I was about seven, a small light microscope from Sears. I still have it and it sits in my office. The cell is beautiful and I’ve always loved imaging sessions,” he shares. “This, coupled with my desire to understand how the machines in our cells work on a molecular level, has driven my research to this day.

Bradley Webb

Chemistry and biology were Bradley Webb ’s best subjects in high school, so he decided to study biochemistry in university. He enrolled in the University of Calgary and studied there for a year before transferring to Queen’s University in Kingston, Ontario. “When I entered university, I had no idea that people got paid to answer questions for a living. I originally intended to go to medical school and become an MD. However, I decided that being an MD wasn’t what I wanted out of my career,” he shares. “Part of the reason for my change of heart was that I was diagnosed with a high-frequency hearing loss in my third year of university and wanted to learn more about what causes diseases on a molecular level.” At that time, he was working on his undergraduate research project in the lab of Charlie Boone (now at the University of Toronto), and found that he really enjoyed doing research. He decided he wanted to pursue a research career. “I approached a faculty member, Alan Mak , whose lectures I really enjoyed and who had an entirely different way of seeing the world, and I convinced him to take me on as a graduate student. The rest is history,” he says. Mak was part of a group that established a protein function discovery center at Queen’s University that had an isother- mal titration calorimeter, an analytical ultracentrifuge, and a biacore, allowing students to biophysically characterize their proteins of interest. Another professor at Queen’s, Michael Nesheim , taught a biophysics graduate course that allowed students hands-on practice with biophysical techniques. “I was very fortunate to be able to get intellectual guidance from both Mak and Nesheim and hands-on access to expensive equip- ment to learn how to use it,” Webb shares. “My overwhelmingly positive experience sparked my interest in biophysics and made me realize the importance of building a ‘toolbox’ of techniques that I can use throughout my career.”

After earning his PhD in biochemistry in 2006, Webb took about nine months off to backpack around Australia and visit his family, then joined Diane Barber’s lab at the University of California, San Francisco, having met her at a conference where he was presenting his graduate research. “Dr. Barber is a pio- neer in developing the field studying how changes in intracellu- lar pH (pHi) impact cell physiology and pathology. Her research is multidisciplinary, highly collaborative research, which aims to achieve atomic-level mechanistic insight into how pHi regulates cell behaviors. I was drawn to the idea that a proton could act as a post-translational modification. My research in Barber’s lab focused on how pHi can regulate pH sensors, proteins with activity or ligand binding that are regulated by physiological changes in pHi. My postdoc career focused on identifying novel pH sensors and designing genetically encoded biosensors for measuring changes in pHi,” he explains. “For example, phos- phofrucokinase-1 (PFK1) can go from completely inhibited to completed activated by changing pH 0.2 units due to proton- ation of a single histidine residue. One of the limitations of studying protonation as a post-translational modification is that we need to have atomic level structures of the molecules to allow us to identify the mechanism of regulation. PFK1 at the time did not have a high resolution biologically relevant crystal structure.” Webb’s group was able to determine the first biologically relevant structure in collaboration with Liang Tong’s group at Columbia University and the Northeast Structural Genomics Consortium. “Brad has two attributes that contribute to his past success and his future promise,” Barber shares. “First, he thinks broadly about cell biology, enabled by his interdisciplinary expertise from protein structure and biochemistry, to cell signaling, to cancer behaviors. Second, he is experimentally fearless, and tackles new approaches and methods without trepidation with the goal of how best to address a question.”

October 2020

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