Different scientific languages, one biomedical question

Adriana Avila-Flores and Wendy Hood look at biology from very different vantage points.

Avila-Flores works at a scale too small to see, designing nanoparticles that can help therapeutic molecules enter cells. Hood takes a wider view, studying how physiology and environment shape variation across individuals and populations.

Their work occupies different corners of biology. But when those perspectives crossed, they opened a new way of thinking about how biomedical research accounts for variation.

The question would eventually bring together four women faculty members in Auburn’s Department of Biological Sciences through an NIH-funded collaboration.

Together, they are exploring whether preserving more biological variation in early stage biomedical research could help scientists better understand the range of responses that may eventually occur in people.

“We want to capture that variation because it’s critically important,” Hood said.

One of the project’s key attributes is genetic diversity. Many traditional laboratory mice models are intentionally highly standardized, helping researchers isolate the effects they are studying. Hood’s wild-derived mouse population, by contrast, maintains substantially more genetic variation — allowing the Auburn team to ask whether that variation reveals response patterns conventional models may miss.

Their collaboration began when Avila-Flores attended one of Hood’s seminars and later visited her research facility. Learning how Hood’s mouse population differed from conventional laboratory models immediately caught Avila-Flores’ attention.

“I need this model for my experiments,” Avila-Flores recalled thinking.

That encounter eventually grew into a broader collaboration with Beth Schwartz, assistant dean for Biomedical Sciences, and Tonia Schwartz, associate professor of biological sciences, adding expertise in immunology and functional genomics.

For Hood, that range of expertise is central to the project.

“I think what’s really important is our diverse backgrounds,” she said.

Following a therapeutic response across biology

Researchers often limit variation in experiments so they can more clearly see how a treatment works. But individuals can respond very differently to the same treatment.

“You respond differently to treatments,” Avila-Flores said. “It’s important to account for that.”

The Auburn team will compare immune-response patterns in conventional laboratory mice with Hood’s wild-derived mouse population. Researchers will then examine how the groups respond to an mRNA-based therapeutic delivery system developed through Avila-Flores’ work.

For Hood, differences among individuals are not simply experimental noise. They can be biologically meaningful — a perspective shaped by her background in ecology and evolutionary biology.

“The humans we ultimately want to help have an ecology as well,” Hood said. “And so your models also need to have an ecology.”

Hood emphasized that conventional laboratory models remain valuable for many scientific questions.

“Laboratory animals are good for asking a lot of questions,” she said. “But they’re not going to be optimal for everything.”

For this project, Avila-Flores is pairing her nanoparticles with messenger RNA, or mRNA.

Although mRNA became widely recognized through its use in vaccines, the molecule has potential applications across a broader range of therapies. The Auburn team will examine responses to the delivery system from several perspectives, including immune activity, gene expression and potential indicators of inflammation.

Together, the four researchers can examine the same question across multiple levels of biology, from the delivery material itself to immune response and patterns of gene expression.

Different perspectives, shared discovery

The project also reflects the breadth of research within the Department of Biological Sciences, spanning molecules and cells to organisms, populations and ecosystems.

Avila-Flores said bringing those perspectives together can change the questions researchers ask and how they approach them.

“I think that’s the way that science finally advances when you have perspectives from different fields,” she said.

Students will experience those intersections firsthand. The NIH grant emphasizes substantial undergraduate participation, and students will contribute to multiple aspects of the project. Data generated through the research also will be incorporated into a functional genomics course, giving additional students experience analyzing data connected to an active research question.

For Avila-Flores, the collaboration reflects one of the department’s greatest strengths.

“The diversity in our department allowed this project to be born,” she said.

Variation makes biology more complicated. But when the ultimate goal is understanding how therapies may perform in people, the Auburn team is asking whether some of that complexity may be exactly what researchers need to see.