Clara Frazier, an IPiB graduate student, will be defending her Ph.D. research on August 2, 2024. Her work in the Weeks Lab sought to expand the ways that scientists can modify proteins to learn more about their function and to engineer new therapeutic functions.
Frazier focused on enzymes found in E. coli that use ATP as an energetic driving force for reactions. She found that the enzyme MccB can use ATP to activate a protein’s C terminus for connection with a broad range of molecules.
“The cool thing about this tool,” says Clara, “is that you can make a handle at the end of a protein that can form bonds very selectively at the C terminus. I like to think of it as a socket. If we use MccB to install the socket at the C-terminus, we can plug in different partner molecules, like peptides or other proteins.
Frazier is especially excited about the versatility that scientists could gain with the ability to add molecules to the ends of proteins, including drugs, fusing proteins with antibodies, and adding modifications to proteins to alter their function. So far, the tool has been tested as a means to attach dye to an antibody in order to track its movement through a cell. As members of the Weeks Lab continue the research that Frazier started, she hopes to see more progress toward therapeutic applications.
Frazier’s work represents essential early steps in the development of such a tool. The ability to start a project from its first inception was one of the things that drew her to the Weeks Lab, which had only just been established when Frazier joined IPiB. Working on a nascent project in a new lab without senior graduate students or postdoctoral researchers gave Frazier welcomed opportunities to problem solve on her own, while knowing she had the support of her advisor to guide her.
“It was a really good balance. I learned any techniques that I had to develop directly from Amy. I also got to figure a lot of things out for myself and build resiliency,” recalls Frazier. “I think in the beginning graduate students can have a lot of fear around the possibility of messing something up. I had the freedom to figure things out for myself and to mess up sometimes and learn that it’s all just part of the process. And now, I really feel confident that I can problem solve and figure out what I need to and accept that there will be mistakes along the way but I’ll get there.”
Frazier found the resiliency and self-confidence she built in the Weeks Lab especially helpful as she mentored undergraduates in her lab and students from the community through Big Brothers Big Sisters of Dane County, as well as her work with the Graduate Leadership and Development Committee (GLDC).
After she graduates, Frazier will take some time to consider how she wants to apply the knowledge and skills she developed in graduate school. She intends to pursue jobs in industry, and is considering a career in which she can apply her skills towards environmental justice work. Frazier began exploring the ways her areas of expertise intersect with environmental justice work during graduate school through volunteer work with Virginia Science – Community Interface, where she interpreted scientific studies as part of an assessment of how natural gas pipelines will impact local communities. She plans to return to the cattle farm in Virginia where she was raised for a few months to reconnect with her region.
To learn more about Frazier’s research, attend her Ph.D. defense, “Developing an ATP-dependent chemoenzymatic tool for C-terminal modification” on Friday, August 2 at 2:00 p.m. CT in Room 1211 of Hector F. DeLuca Biochemical Sciences Building.