Professor Katherine McReynolds’ team of chemistry students hasn’t cracked the case on HIV prevention yet, but it’s getting closer in a beaker-strewn lab on the California State University, Sacramento, campus.
The students spend 40 to 60 hours each week creating new chemical compounds. The goal is to find a group of molecules that can bind to protein structures on the surface of HIV cells, which would prevent the virus from infecting the host cells.
“It’s a blocking agent – like a molecular decoy,” McReynolds said. “(The virus) won’t be able to see the structures on the host cell because it’s been bound up with our molecule. Being able to block infection before it happens would be a really good thing to be able to do.”
McReynolds, who has been working on the project since she arrived on campus 15 years ago, received a $425,000 grant from the National Institutes of Health on April 1 that will sustain her research for the next four years. The funding comes from the federal Support of Competitive Research program, or SCORE, which aims to boost research at institutions serving students typically underrepresented in the biomedical field.
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Sacramento State is newly eligible for SCORE funding, having been declared a Hispanic-Serving Institution by the Department of Education in 2015. That award is often reserved for schools that are primarily teaching institutions or don’t have a long history of aggressive grant pursuits, said David Earwicker, associate vice president of the Office of Research Affairs at Sacramento State.
After an arduous application process, McReynolds’ project was selected from a pool of other schools that fit the criteria. As the first of its kind at Sacramento State, the SCORE award elevates research visibility for the entire campus, Earwicker said. It also marks a new era for the National Institutes of Health as it widens access to academic funding beyond Ivy League colleges.
“By getting funded by this particular funding source, we’re now classified in NIH as a minority-serving institution, which gives us access to different resources and funds we can apply for,” he said. “This signals to the campus that NIH is going to be a bigger partner in the future.”
This signals to the campus that (the National Institutes of Health are) going to be a bigger partner in the future.
David Earwicker, associate vice president of the Office of Research Affairs at Sacramento State
The funding comes at a crucial time for HIV research, as rates of infection remain high, particularly among transgender women and young men. A drug called Truvada recently received Food and Drug Administration approval and is being adopted as a public health prevention strategy. Truvada, which comes as a pill, prevents HIV infection by creating a protective shield around the T-cells.
The virus-disabling compounds created by McReynolds and her students are carbohydrate-based macromolecules. They are made by adding carbohydrate structures to sugar-containing polymer molecules. McReynolds’ research specifically targets the GP120 protein on the outer layer of the HIV cell.
Ultimately, the structures could be formulated into a topical drug, to be applied to the skin. But before it moves toward clinical trials, the team needs to get its compound recipe just right.
“We’ve changed the design and tried to make them better, so that they’re more potent and have better activity,” she said. “This is organic chemistry at its finest.”
The new funding will enable McReynolds to add two students to her seven-student team – a mix of undergraduate and graduate students who work under her supervision. She assigns each student a project based on the combinations in her proposal, which must remain confidential due to the terms of the grant. The students plan out and conduct their reactions in a special microwave, purify the product away from the solvent, usually water, and test it for its chemical makeup.
Ella Mokrushin, a Sacramento State senior who has been working with McReynolds since December, said she appreciates having the independence to conduct her own reactions and is determined to keep experimenting, even when it means clocking long hours of lab time on top of classes and homework.
“The process of reactions and identifying what you have really drives you,” she said while peering into a test tube on a recent lab day. “That’s the exciting part – trying to figure out what did you make? And did it work?”
If a student’s molecule looks promising, McReynolds tests it against a lab-created version of the protein that would be found on the surface of HIV cells to see if the molecule can bind to the protein efficiently. If it passes that test, she sends it to Duke University, where scientists can evaluate the molecules against HIV to determine if the molecules can prevent the cells from being infected. From that multistage process, the team has found about 10 with moderate anti-HIV activities.
The communication and the quality of the science has been outstanding.
Celia LaBranche of Duke University, on McReynolds’ HIV-fighting molecules
Celia LaBranche, who helps oversee virus neutralization services at Duke and has been working with McReynolds’ samples, said that she has seen great progress in the samples over the last few years and that the “communication and the quality of the science” from Sacramento State has been “outstanding.”
“When she first started, her compounds were only mildly inhibitory, and that’s very common as investigators try to develop HIV-neutralizing compounds or strategies,” LaBranche said. “Her compounds have gotten more potent.”
Editor’s note: This story was changed Tuesday to reflect that the group of molecules sought by the California State University, Sacarmento team would prevent HIV from infecting host cells, not just T-cells.