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College of Arts and Sciences

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Arts and Sciences boasts trio of MIRA winners

Earning the Maximizing Investigators’ Research Award is a rare accomplishment. The MIRA is a prestigious honor bestowed annually by the National Institute of General Medical Sciences, part of the National Institutes of Health, and only those researchers at the cutting edge of their field are considered.

But at the College of Arts and Sciences, where all incoming faculty are paired with skilled mentors and college leadership is highly supportive throughout the grant process, three researchers have secured MIRAs to fund their innovative lab research into fundamental sciences.

Caryn Outten, professor of chemistry, is in her eighth year of receiving funds through the award for established investigators, while professor of evolution and plant biology, Carolyn Wessinger, and professor of biochemistry and molecular biology, Jie Li, are in the third and second year, respectively, of funding for early-stage investigators.

Caryn Outten, Department of Chemistry and Biochemistry, Established Investigator MIRA

In Caryn Outten’s lab, baker’s yeast can be found in abundance, but Outten isn’t studying food. She’s interested in how biological systems use essential metals — iron, zinc and copper — to perform a variety of different life functions.

Outten’s research unites her expertise in how microbes sense and regulate iron levels with the complexities of yeast genetics. As it turns out, the fungi responsible for leavening bread are also ideal models to study cellular function, and Outten’s senior MIRA award is allowing her to do just that. More recently, she has been studying pathogenic fungi that cause human infections.

At the cellular level, battles take place every day within our bodies between microorganisms found in the environment and our immune systems. Our cells need iron to function, but so do the invading pathogens, from the yeast that causes thrush to mold spores inhaled from decaying matter in soil that cause lung infections. While our immune systems rush to stow away essential metals in inaccessible proteins and cells, invading pathogens send out their own molecules that tightly bind and retrieve iron from the bloodstream.

“Our role is to understand how they do that,” Outten says. “What are the mechanisms at the molecular level for controlling iron in the organism?”

The MIRA grant has been invaluable in Outten’s work, funding her lab and students as they culture cells and yeast, study their growth rates and purify the proteins whose structures and functions they hope to analyze.

“These organisms [yeast] can cause infections,” Outten says. “If we can better understand how they acquire and regulate iron and the roles of individual proteins, we can exploit this information to develop compounds that target those proteins. The goal is to limit their access to this essential nutrient to prevent infections from happening.”

Jie Li, Department of Chemistry and Biochemistry, Early-Stage Investigator MIRA

Jie Li is a pharmaceutical scientist by training. With his early investigator MIRA and additional expertise in biochemistry, Li is working to mine the genomes of microbes for molecules that can be used for drug discovery, much like the penicillin molecules naturally produced by fungi.

By looking at the sequence of genes in different microbes, Li and his team are hoping to pinpoint specific enzymes and biological responses that offer promising results for pharmaceutical development.

“We use genome sequence information to unlock the hidden chemistry there,” Li says. “Different sequences mean they will encode enzymes that will do different types of chemical reactions. By looking at the gene sequences, we can predict what compounds could be made.”

Two years into the grant, Li has already identified two major molecules with implications in the world of medicine: a lipid molecule produced by bacteria in the gut whose anti-inflammatory qualities could combat IBS, and a class of molecules called lanthipeptides that has anti-microbial properties. He also has several patent applications in the works.

Li is quick to emphasize the multidisciplinary, collaborative nature of his research, which involves big data analysis, genomics, molecular biology, microbiology and enzymology. The questions he wants to pursue stretch far beyond biochemistry, and Li credits the scale of his success to the robust partnerships he’s developed with peers across campus.

“I collaborate a lot with my colleagues in biological sciences and the School of Medicine. They have been so supportive and helpful for my research to go forward,” Li says. “I really appreciate their help.”

Carrie Wessinger, Department of Biological Sciences, Early-Stage Investigator MIRA

Understanding convergent evolution — how the same traits evolve across separate lineages, such as the development of wings in both birds and bats — is a key factor in unlocking the secrets of evolutionary biology. For Carrie Wessinger, the search for answers finds a natural outlet in perennial wildflowers.

“Plants are a really convenient system for studying the genetics of adaptive evolution,” Wessinger says. “They’re easy to raise, they stay in one place, and it’s easy to do controlled mating between them by crossing.”

With her MIRA grant, Wessinger has been working with her team to better understand how flowers have repeatedly evolved over time to develop traits adapted to hummingbird pollination: bright red flowers, narrow tubular shapes, large amount of nectar, and elongated stamens and styles that brush the foreheads of hummingbirds as they drink nectar.

Wessinger’s lab group frequents high-elevation areas in the southwest and Rocky Mountains, collecting specimens for DNA extraction and sequencing genetic data to identify patterns in how genes are expressed. Relying on information about the current set of species in the group of plants they study, Wessinger’s team is able to infer the evolutionary history of the flowers, capturing a clearer understanding of how they have selectively adapted over time to pollination by hummingbirds.

Yet the answer remains complicated.

“Are the same types of genes responsible for these separate shifts in different types of hummingbird-pollinated flowers? We’ve found cases of yes and no,” Wessinger says. “We have some traits that tend to involve similar mutations to the same exact gene.”

The potential implications of Wessinger’s research provide extra incentive to continue seeking answers. “Why are some genetic changes predictable whereas others involve really idiosyncratic changes? That’s what we’re working on at this point,” she says. “I believe that what we find can be extrapolated to any kind of complex adaptation.”

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