Ph.D. student uses computational biochemistry to tackle neurodegeneration, cancer, and premature aging
April 25, 2019
In December 2018, Alexa Salsbury, a Virginia Tech graduate student in the Department of Biochemistry, received the Bruce M. Anderson Graduate Award for the Outstanding First-Year Biochemistry Graduate Student.
“When I heard I had received the award, it was unexpected but validating. It meant a lot to me because I really respect the other people in my graduate cohort and department,” said Salsbury.
Salsbury is working in the lab of Justin Lemkul and pursuing her interests in computational biochemistry. She is performing molecular dynamics simulations on DNA G-quadruplexes to gain a better understanding of their dynamics and folding. G-quadruplexes are DNA structures that are rich in guanine, one of the four bases found in DNA. DNA G-quadruplexes serve as regulators of gene expression and altered stability, and their formation is linked to a number of diseases, ranging from mental retardation and neurodegeneration to several types of human cancer.
Salsbury is first author of a paper recently published by the Lemkul lab in The Journal of Physical Chemistry B that examines a gene required for blood vessel development in tumors having two G-quadruplexes in their promoter region. Salsbury identified these G-quadruplexes as potential targets for pharmaceutical development to turn off this gene entirely.
“Alexa's research has the potential to provide critical details about new molecular targets for drugs against a variety of human diseases. She works diligently to describe detailed interactions within DNA G-quadruplexes to provide unprecedented insights,” said Lemkul, an assistant professor in the Department of Biochemistry in the College of Agriculture and Life Sciences.
Originally from a rural area in Ohio, Salsbury is a first-generation college student. As a child, she wanted to become a medical doctor, but through her undergraduate education and research at Eastern Michigan University, she realized there were many other career possibilities in science that contribute to the medical field.
It was Virginia Tech’s strong reputation as a university, as well as its vast abundance of research opportunities, that brought her to Blacksburg as a graduate student. She instantly felt connected with the biochemistry department. “There was a combination of camaraderie and mentorship that I felt I would get in a small department, but I'd also have access to all the resources of a big university,” Salsbury said.
However, her academic aspirations didn’t stop there.
Her first introduction to computational biochemistry was through multiple lab rotations in the biochemistry department. At the time, Lemkul was beginning projects on G-quadruplexes. In his post-doctoral position, Lemkul helped create and refine a groundbreaking polarizable force field for DNA that is part of a software program in molecular dynamics. Salsbury said that its significance in drug design and therapeutics combined with her mentor’s passion for the work drew her toward the Lemkul lab and G-quadruplex research.
Currently, the Lemkul lab is working on two distinct projects involving computational biochemistry, one involving Salsbury’s G-quadruplex research and the other involving simulations of amyloidogenic proteins, which is a collaboration with Anne M. Brown, an assistant professor in research and informatics in the University Libraries and an adjunct professor in the Department of Biochemistry in the College of Agriculture and Life Sciences.
To better understand how G-quadruplexes and their stability play a role in disease, Salsbury is applying a polarizable force field to these biomolecules. The theory behind the work is extracted from the disciplines of quantum mechanics, physics, and physical chemistry.
The methodology of the Lemkul lab’s research is new because they are the first to apply polarizable force fields to provide a better model of G-quadruplexes. The Lemkul lab is using these polarizable force fields in simulations to understand factors that stabilize the structure so they can eventually understand how to design molecules that bind to it. This ongoing lab work is being led by Salsbury.
Molecular dynamics simulations can provide valuable scientific data and visualizations to both bench biochemists and medicinal chemists.
“Molecular dynamics makes the discovery or process of understanding a complex phenomenon more affordable,” Salsbury said. “In terms of the drug market, it can reduce the cost and energy that goes into the process of developing new therapeutics, which, in turn, should make therapeutics cheaper for consumers.”
Asked about the favorite part of career, Salsbury said, “Computational research can really help accelerate research and scientific discovery. Advocating for the computational research field and helping people utilize the tools that are available is what I see for myself in the future.”
Salsbury also participates in various computational outreach activities. The Practice & Experience in Advanced Research Computing Conference (PEARC) is an annual meeting that provides a forum for discussing challenges, opportunities, and solutions among the broad range of participants in the research computing community. Salsbury’s involvement with PEARC was sparked by a seminar provided by the Department of Biochemistry. At that seminar, a National Science Foundation (NSF) program officer spoke about NSF’s mission and vision to promote the progress of science through research and outreach. Salsbury approached Anne M. Brown about computation-centered outreach efforts that would allow her to engage underrepresented youth, like herself, in STEM (science, technology, engineering, and mathematics).
Every year, Salsbury and Brown perform outreach with Virginia Tech’s HyperCube, an immersive visualization environment that projects anything from DNA strands to intricate networks of neurons in a large 10-by-10 room.
This past year, Salsbury received the award for best student paper at the PEARC conference titled, “Using Immersive Visualization Environments to Engage Students in Hands-on Learning.”
"Our ability to engage in outreach experiences like the one in the HyperCube highlights our dedication to Virginia Tech's land-grant mission by providing routes to connect with students and highlight the connection between 'cool' technology and science. Alexa's outreach work demonstrates areas of science and research in new ways, hopefully sparking interest and increasing accessibility to all students," said Brown.
The HyperCube attracts kids and higher achievement groups from all over the nation, as well as others who have an inherent desire to learn more about science, something Salsbury can identify with. “Being from a family without a lot of college or research experience, it was really cool to talk to the kids and hear, ‘Oh, I want to be a scientist when I'm older.’ And I can ask, ‘Okay, what kind of scientist? A researcher?’ Questions that people never asked me, and I didn’t ever really think about.”
-Written by Kendall Daniels