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Even negative research findings can take new, exciting paths, Mark Hargrove and fellow researchers found. Though their research funded by the Signature Research Initiative showed no promise for helping animal cells survive during and after low oxygen conditions, the chemistry led them to new, potentially groundbreaking research in fertilizer production.

“This type of funding allows you to be more nimble in the directions that you take,” Hargrove said. “The ability to stop and say ‘this is our original applied idea, but the basic science says it needs to go here, this is where the impact is,’ I think that’s the way basic research has to be done.”

The Liberal Arts and Sciences Signature Research Initiative (SRI) was designed to encourage LAS faculty to develop and lead interdisciplinary, collaborative research projects with the goal of enhancing the international visibility and impact of LAS-led research and to increase the College’s sponsored research expenditures.

Hargrove, along with co-investigators Amy Andreotti, professor in the Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology; Jo Anne Powell-Coffman, professor and chair of the Department of Genetics, Development, and Cell Biology; and Robert Jernigan, professor in the Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology were investigating how plant cells can survive longer than animal cells without oxygen and whether plant methodologies could be used to enhance the ability of animal cells to survive in oxygen deprived states — important for stroke or heart attack treatment.

Plant cells have an increased ability to survive long periods without oxygen, due to their ability to use plant hemoglobin to capture displaced electrons for specific chemical reactions. This reduces the production of toxic chemicals in the cell when oxygen, which is highly reactive, is reintroduced. Introducing plant hemoglobin into animal cells showed no benefit to the animal cells, but understanding the chemistry behind the plant hemoglobin led to interest in nitrogen fixation, the process by which nitrogen is made available to living organisms.

“It is probably the single most important industrial reaction that humans have developed in the last hundred or so years,” Hargove said.

The reaction converts dinitrogen, the form of nitrogen that is abundant in the atmosphere, to ammonia and other nitrogenous molecules that can be used for fertilizer. Discovery of this reaction in the early 1900’s created the green revolution, said Hargrove, allowing modern agricultural techniques to sustain a larger human population all over the world. However, the process takes a lot of energy and uses resources that are not sustainable. Due to this, there has been much recent interest in finding low energy alternatives, such as a biochemical mimic of this industrial reaction.

“What we were doing already that we thought was sort of esoteric chemistry was actually on the cutting edge of nitrogen fixation mimics,” Hargrove said. “If you look at what the chemists are trying to do, they would love to have some of the properties of the system we have working in their systems. So we just had to make that realization.”

The key factor that makes the reaction challenging is how unreactive nitrogen is, which is what Hargrove and his fellow researchers are working on now. Through modifying the structure of the protein, they are attempting to increase its reactivity with dinitrogen.

“Getting it started is the trick — that’s the hurdle that everybody faces in trying to do this,” Hargrove said. “If we can get it started our protein can do the rest of the steps of the reaction.”

This story is one of three updates on research projects awarded LAS Strategic Research Initiative funds in 2014.