This spotlight was contributed by Kelvin P. Idanwekhai, a graduate student communicator at UNC studying Biophysics and Chemistry. He recently joined Alex Tropsha’s lab at the School of Pharmacy.
If you hang around the bio-focused students at UNC long enough, you will hear words like “protein” or “small-molecule” thrown around in almost any conversation. They are a big deal for biochemists and biophysicists, given that most things in our bodies are proteins, antibodies, enzymes, collagens, hormones, and others. Most people know that nature produces proteins; however, they can also be engineered to work faster or serve as better therapeutics. Researchers at the Kulman lab spend most of their days thinking about proteins, how to design them, and how to improve them.
In a conversation with Amelia McCue, a 5th-year Ph.D. student in the lab, we tried to unravel what the lab is currently working on. Her work centers on targeted drug delivery, and the big problem she tries to solve involves the design of antibodies that can bind two different things (bi-specific antibodies).
The design of this protein is difficult because she wants it to be activated only inside the tumor cells and not outside to avoid a long list of side effects. “I am trying to use a protein engineering approach to control the activity of that antibody drug to perform its therapeutic effect in the tumor,” she tells us.
We also tried to get a sense of what her colleagues worked on, and she said, “Everybody in the lab does something a little bit different; some people are doing basic protein design, but mine is towards a biomedical application. One of my lab mates designed a faster enzyme, which was not something you would immediately think about putting in patients. It is just a cool design goal and feat.”
She talked about some of the recent advancements in the field and how they are impacting research at the Khulman lab; “It has been an interesting time since I joined the lab because we were always primarily using this software called Rosetta, which is a physics-based tool used to design proteins; it is also used to predict protein structure; however, over the past few years, AlphaFold and other machine algorithms have been developed that are competitive, if not better than some of the methods that we have used. AlphaFold has been great for structure prediction, but it is also now used for design. Some of my peers in the lab are much more computational and have developed machine-learning pipelines for someone like me, who is a bit more hybrid and works at the bench doing experiments for protein design. However, it has been exciting to play with some of these tools and pipelines my labmates have designed. “
We asked Amelia if UNC was the best place for the research she was doing right now, to which she responded, “Absolutely! I am happy to be here, for several reasons. First, the science and community at large, UNC is full of great people. I feel fortunate to have chosen here for graduate school because I am someone who thinks if the environment is not great and I am not happy, I might not do very well. My laboratory environment and the greater UNC community have been supportive of me. Nothing is perfect, but it’s good, and I am happy here. I came in with an undergraduate degree in chemistry and wanted to be a little bit closer to biomedical research in my Ph.D., and right now I think I have done that.”
She also talked about how being close to the UNC Hospital and the cutting-edge School of Medicine helped her develop amazing scientific collaborations and has collaborated with people in the HIV center, and some of her lab mates have collaborated with people doing clinical trials at UNC.