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Biophysicist in Profile

Bradley Webb

Bradley Webb

October 2020 // 2580

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.

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 isother­mal 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 equip­ment 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 pio­neer in developing the field studying how changes in intracellu­lar 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, phos­phofrucokinase-1 (PFK1) can go from completely inhibited to completed activated by changing pH 0.2 units due to proton­ation 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.”

Bree Grillo-Hill, a postdoc coworker of Webb’s in Barber’s lab, shares, “Brad’s innate curiosity makes him stand out as a sci­entist. His broad interests across different fields of cell biology have led him to a really unique set of research objectives. He is always open to new ideas, and excited to use innovative techniques to address important problems. He challenges everyone around him by asking really tough, deep questions in the most friendly manner to really encourage conversations about science.”

Webb’s lab at West Virginia University studies how metabolic enzymes are organized in the cell, how they are spatially and temporally regulated, and how they can be dysregulated in diseases. “We work on multiple scales — from structure and function analysis to obtain atomic level understanding of how these molecular machines work, to characterization of meta­bolic enzymes in vitro, and to determine their organization and regulation in cells. We are currently focusing on enzymes in the glycolytic pathway and are generating tools to determine the spatiotemporal regulation of glycolysis in the cells and how metabolic reprogramming contributes to diseases such as cancer,” he shares.

The biggest challenge of Webb’s career has been finding success in the face of his disability. After being diagnosed with high-frequency hearing loss in his third year of undergraduate studies, his grades improved — he was now receiving the help he needed. “If you think of how much of science is transmitted orally — lab meetings, seminars, classes — it was a major barrier to my ability to fully participate,” he says. By the time he was a postdoc, he had lost enough of his remaining hear­ing that he needed a cochlear implant. “Coming from Canada, where healthcare is universally celebrated as a human right, I had a very rude introduction to the American medical insurance system. As a postdoc I needed to fight to obtain insurance coverage to pay for the operation. I was denied coverage three times and was very close to leaving my postdoc to move back to Canada so I could get the help I needed. Without help from a lot of great people I am certain I would no longer be in research,” he shares. “My postdoc mentor, Diane Barber, was an outstanding advocate and supported me significantly throughout the ordeal. I would not be where I am today without her financial, professional, and emotional support.”

After the initial operation to insert his implant, he was essen­tially deaf for about four weeks until the implant was activated. Upon activation, he had to relearn how to hear. “It took me about six months before I was able to understand voices clear­ly, two years until I felt comfortable in seminar type situations, and about five years before I started to enjoy music again. My hearing is still an obstacle as I do not hear ‘normally.’ Loud noises and background noise, such as a busy restaurant, make it almost impossible for me to listen effectively,” he explains. “In my teaching, my first slide always describes my hearing loss so I can let students know how best to communicate with me. Wearing masks to slow the transmission of COVID-19 is also a challenge as it prevents speech reading, making communica­tion more difficult for those of us with hearing loss. One thing I have noticed is that there are not a lot of disabled people in leadership positions in academia. Looking back on my under­graduate and graduate training, I cannot remember taking a class from a single professor with a physical disability.”

Like many others during the COVID-19 pandemic, Webb and his wife have lost childcare for their two-year-old. “It has been ex­traordinarily difficult to find a work-life balance and to maintain productivity,” he shares. “West Virginia University in general and my department specifically have been very supportive of junior faculty, which I am deeply appreciative of.”

Rather than traveling farther afield, Webb and his family have been exploring West Virginia during this period of social dis­tancing. “We recently took my daughter, who is two, camping for the first time and she loved it!” he says. “We are looking forward to getting a chance to see more of this beautiful state. My daughter also makes sure that we take the opportunity to visit as many playgrounds as possible.”

Webb offers three pieces of advice for early career biophysi­cists: “First is to ‘run your line,’” he says, offering a North Amer­ican football metaphor. “You need to run where you need to be to tackle the ball carrier, not to where the ball carrier is when you start. The line you need to take constantly changes, so you will always need to take in the new information and adapt.[…] Don’t fret if it takes you longer to get there than other peo­ple, due to personal choices, extenuating circumstances, or a personal setback. Just run your line and you will be successful. The second is to surround yourself with good people. No one is successful alone, having a good support network of people who will raise you up, fight for you, and challenge you to succeed is essential. The third is to be experimentally fearless. Fall in love with a question and then use whatever techniques you need to learn to answer it.”

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