Research synergy produces unique, exciting results
Within his successful National Science Foundation CAREER award proposal, Dmitry Korkin, a University of Missouri assistant professor of computer science, included his intent to apply his work in structural bioinformatics to the study of nematodes.
His collaboration with molecular nematologist Melissa Mitchum, an MU associate professor of plant sciences, has been fruitful. The pair had co-authored two journal papers when she approached Korkin with another project.
“Melissa’s group and their collaborators at Southern Illinois University had identified a gene in soybeans with natural mutation causing resistance to nematodes, one of the main soybean parasites. However the molecular mechanisms behind this resistance were still a mystery,” Korkin said.
Korkin engaged the help of Samantha Warren, a bioinformatics graduate student in his lab who has an extensive background in biochemistry. They began by modeling the protein, an enzyme, and discovered it actually was a dimer, or two identical proteins.
“It’s very common for proteins to interact with themselves to perform a certain function,” Korkin said adding that they then needed to model the complex.
“There are levels of complexity which makes this research more exciting. It’s cool because you learn so much. Every day you learn something,” he said.
They began by mapping all known information about the function of the gene — locating all regions that are responsible for a certain function. What they found was a small chamber, hidden within the dimer, that binds organic molecules important for metabolic reactions.
“Even more interestingly, when we mapped those natural mutations, they were all located near the chamber,” Korkin said.
“We realized they were on the surface, co-localized with functional regions. That gave us a clue. It gave us a good sense of how the resistance mechanism works and a place to start research,” he added.
Korkin said in bioinformatics, scientists often work on self-contained projects.
“In my view, there is something missing from such an approach,” he said. “This project, in contrast, demonstrates the perfect synergy.
“There are a set of proposed experiments and a hypothesis. We provide the structural insights and link it to the functional mechanisms so our experimental colleagues can test the hypothesis,” Korkin said. “This synergy saves time and streamlines the process.”
While plant geneticists in pursuit of nematode resistant soybean varieties may immediately utilize the discovery, it will take more time for Mitchum’s research group and their collaborators to unwind the mystery of the enzyme’s activity.
A paper detailing the work appeared in the journal Nature.